==================================BSR12================================== 12. Cell mediated immune response against malaria: - antibody mediated cytotoxicity - T cell cytotoxicity - T soluble factors generated after the infection - The effect of Interferon IL2, IL1, BCDE on the immunity against malaria. 1 UI - 87117224 AU - Brown J ; Greenwood BM ; Terry RJ TI - Cellular mechanisms involved in recovery from acute malaria in Gambian children. AB - This paper reports the results of in vitro experiments which attempt to elucidate the mechanisms whereby Gambian children control acute infections of Plasmodium falciparum. It was shown initially that mononuclear cells from children with acute malaria, in the presence of specific antibody, caused a marked reduction in in vitro parasite growth. IgM antibodies appeared to be considerably more effective than IgG. T or B lymphocytes were ineffective in the system; adherent cells alone had some effect, but much less than the unfractionated cell population. Adherent cells were however fully effective after exposure to supernatants from T cells activated either non-specifically by phytohaemagglutinin (PHA), or specifically by P. falciparum antigens. Depression of parasite growth was also observed, independent of anti-malarial antibody. This was achieved when adherent cells from healthy Europeans, as well as those from infected children, were exposed to the supernatants from previously stimulated T cells before adding to the culture. Furthermore, intra-erythrocytic parasite death occurred after a short exposure to the supernatants of 'activated' adherent cells from both infected children and Europeans. MH - Adolescence ; Adult ; Antibody-Dependent Cell Cytotoxicity ; B Lymphocytes/*IMMUNOLOGY ; Cell Adhesion ; Child ; Child, Preschool ; Comparative Study ; Europe/ETHNOLOGY ; Gambia ; Human ; IgG/ANALYSIS ; IgM/ANALYSIS ; Infant ; Lymphocyte Transformation ; Malaria/*IMMUNOLOGY ; Middle Age ; Monocytes/IMMUNOLOGY ; Plasmodium Falciparum/IMMUNOLOGY ; T Lymphocytes/CYTOLOGY/*IMMUNOLOGY SO - Parasite Immunol 1986 Nov;8(6):551-64 2 UI - 87103752 AU - Taverne J ; Treagust JD ; Playfair JH TI - Macrophage cytotoxicity in lethal and non-lethal murine malaria and the effect of vaccination. AB - We investigated the development of cell-mediated immunity in lethal and non-lethal malarial infections by assaying the cytotoxic activity of spleen cells for L929 tumour cells at different times after infection of mice with the lethal P. berghei, a lethal variant of Plasmodium yoelii and the non-lethal P. yoelii and P. chabaudi. In all cases the cytotoxicity increased to a peak during the first week and then diminished but the time of the peak varied with the infection; its activity was lowest with P. berghei. A second peak occurred in the non-lethal infections at the time of recovery. A protective vaccine accelerated and enhanced the early peak of cytotoxicity. The activity was mediated by adherent phagocytic cells, probably through the release of tumour necrosis factor (TNF) by macrophages since it was inhibited by antiserum against recombinant mouse TNF and did not destroy TNF-resistant L929 cells. Its induction was not dependent on T cells since it occurred in T cell-deficient mice infected with non-lethal P. yoelii. However, the accelerated increase associated with vaccination could be adoptively transferred by spleen lymphocytes from vaccinated mice. MH - Animal ; *Cytotoxicity, Immunologic ; Female ; Immunization, Passive ; Macrophages/*IMMUNOLOGY ; Malaria/*IMMUNOLOGY ; Mice ; Mice, Nude ; Plasmodium Berghei ; Spleen/IMMUNOLOGY ; Support, Non-U.S. Gov't ; T Lymphocytes/IMMUNOLOGY ; *Vaccination SO - Clin Exp Immunol 1986 Oct;66(1):44-51 3 UI - 87069926 AU - Miller LH ; Howard RJ ; Carter R ; Good MF ; Nussenzweig V ; Nussenzweig RS TI - Research toward malaria vaccines. AB - Malaria exacts a toll of disease to people in the Tropics that seems incomprehensible to those only familiar with medicine and human health in the developed world. The methods of molecular biology, immunology, and cell biology are now being used to develop an antimalarial vaccine. The Plasmodium parasites that cause malaria have many stages in their life cycle. Each stage is antigenically distinct and potentially could be interrupted by different vaccines. However, achieving complete protection by vaccination may require a better understanding of the complexities of B- and T-cell priming in natural infections and the development of an appropriate adjuvant for use in humans. MH - Antigenic Determinants/ANALYSIS ; Arthropod Vectors ; Erythrocytes/ PARASITOLOGY ; Helper Cells/IMMUNOLOGY ; Human ; *Immunotherapy ; Malaria/ IMMUNOLOGY/*PREVENTION & CONTROL/TRANSMISSION ; Molecular Weight ; Mosquito Control ; Plasmodium/IMMUNOLOGY ; Receptors, Antigen, T-Cell/ IMMUNOLOGY ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, Non-P.H.S. ; Support, U.S. Gov't, P.H.S. ; *Vaccines SO - Science 1986 Dec 12;234(4782):1349-56 4 UI - 87069572 AU - Merino F ; Layrisse Z ; Godoy G ; Volc:an G TI - Immunoregulatory alterations in Plasmodium falciparum and Plasmodium vivax infections. AB - Studies on the immune function of patients with acute Plasmodium vivax or P. falciparum infections were performed. All subjects were residing in recent malaria endemic areas of Venezuela. Lymphopenia, reduction of peripheral blood T-lymphocytes positive for monoclonal antibody OKT4 (T helper) a decrease of in vitro mitogenic proliferative response and natural killer cell activity were observed. Serum lymphocytotoxic antibodies reactive at 37 degrees C were detected in both groups of patients as well as serum autoantibodies. The possible role of lymphocytotoxic autoantibodies in the etiology of the T-lymphocyte depletion and acquired immunological perturbations in human malaria is discussed. MH - Antilymphocyte Serum/*ANALYSIS ; Helper Cells ; Human ; Killer Cells, Natural/IMMUNOLOGY ; Leukocyte Count ; *Lymphocyte Transformation ; Lymphocytes/*IMMUNOLOGY ; Lymphopenia/ETIOLOGY ; Malaria/*IMMUNOLOGY ; Plasmodium Falciparum ; Plasmodium Vivax ; T Lymphocytes SO - Trop Med Parasitol 1986 Sep;37(3):241-4 5 UI - 87045591 AU - Ballet JJ ; Druilhe P ; Brasseur P ; Looareesuwan S ; Chantavanich P ; Tharavanij S TI - Influence of circulating malarial antigens on cell mediated immunity in acute Plasmodium falciparum malaria. AB - In a group of Thai patients with P. falciparum acute malaria, circulating malarial antigens (CMA) were detected in 27/33 cerebral malaria (CM) cases and 31/43 noncerebral cases. Delayed cutaneous responses to phytohemagglutinin and candidin were found frequently negative in patients with CMA, especially in the CM group. Mean in vitro lymphocyte proliferative responses to lectins were lower in the group of patients with CMA. An inhibitory activity on proliferative responses to phytohemagglutinin of lymphocytes from healthy individuals was exerted by sera containing CMA. Data suggest that CMA from P. falciparum may suppress in vivo and in vitro cell mediated immune reactions. MH - Acute Disease ; Adolescence ; Adult ; Aged ; Antigens, Protozoan/ANALYSIS/ *IMMUNOLOGY ; Child ; Female ; Human ; IgG/ANALYSIS ; IgM/ANALYSIS ; Immunity, Cellular ; Lymphocyte Transformation ; Malaria/*IMMUNOLOGY ; Male ; Middle Age ; Plasmodium Falciparum/*IMMUNOLOGY ; Skin Tests ; Support, Non-U.S. Gov't SO - Acta Trop (Basel) 1986 Sep;43(3):255-62 6 UI - 87032169 AU - Orago AS ; Solomon JB TI - Antibody-dependent and -independent cytotoxic activity of spleen cells for Plasmodium berghei from susceptible and resistant rats. AB - Antibody-dependent cell cytotoxicity (ADCC) mediated by spleen cells from 30- or 50-day old rats against 51Cr-labelled rat erythrocytes parasitized by Plasmodium berghei in the presence of anti-P. berghei antibody showed only slight age differences. However, in the absence of specific antibody, the total cell-mediated cytotoxicy (CMC) per spleen was four times higher in the spleen cells from 50-day-old rats compared with those from 30-day-old rats. CMC accounted for about 50% of total cytotoxic activity in 50-day-old rat spleens. Spleen cells mediating ADCC and CMC are Thy-1.1 positive, and those mediating ADCC are nearly all non-adherent to Sephadex G-10 columns. MH - Aging ; Animal ; Antibody Formation ; *Antibody-Dependent Cell Cytotoxicity ; *Cytotoxicity, Immunologic ; Disease Susceptibility ; Erythrocytes/IMMUNOLOGY ; Female ; IgG/IMMUNOLOGY ; Immunity, Natural ; Malaria/*IMMUNOLOGY ; Plasmodium Berghei/*IMMUNOLOGY ; Rats ; Spleen/ *IMMUNOLOGY ; Support, Non-U.S. Gov't SO - Immunology 1986 Oct;59(2):283-8 7 UI - 87032168 AU - Solomon JB TI - Natural cytotoxicity for Plasmodium berghei in vitro by spleen cells from susceptible and resistant rats. AB - The susceptibility of 30-day-old rats to Plasmodium berghei infection has traditionally been ascribed to the higher levels of circulating blood reticulocytes for which P. berghei has a predilection. However, spleen cells soon develop natural cytotoxicity for P. berghei which may account, in part, for the increased natural resistance of older rats. Spleen cells from normal 30- or 50-day-old rats were cultured overnight with erythrocytes parasitized by P. berghei and then injected into MF1 mice. Six days later, the percentage parasitaemia was determined and the extent of killing by the spleen cells in vitro determined. Spleen cells from 50-day-old resistant rats were found to be four times better at killing P. berghei in vitro than those from 30-day-old susceptible rats. Antibody-dependent cell cytotoxicity (ADCC) was, at best, only a minor component. About 12% of total cytotoxicity was destroyed by pretreatment of spleen cells with monoclonal anti-Thy-1.1 antibody and complement. The possibility that natural cytotoxicity in these experiments is mediated by natural killer cells is discussed. MH - Animal ; Antibody-Dependent Cell Cytotoxicity ; Cells, Cultured ; Complement/IMMUNOLOGY ; Cytotoxicity, Immunologic ; Disease Susceptibility ; IgG/IMMUNOLOGY ; Immunity, Natural ; Isoantibodies/ IMMUNOLOGY ; Malaria/*IMMUNOLOGY ; Plasmodium Berghei ; Rats ; Spleen/ *IMMUNOLOGY ; Time Factors SO - Immunology 1986 Oct;59(2):277-81 8 UI - 87009883 AU - Grau GE ; Piguet PF ; Engers HD ; Louis JA ; Vassalli P ; Lambert PH TI - L3T4+ T lymphocytes play a major role in the pathogenesis of murine cerebral malaria. AB - The pathogenic importance of L3T4+ T cells in the development of murine cerebral malaria was demonstrated by the following observations. First, in vivo administration of an anti-L3T4 monoclonal antibody protected Plasmodium berghei-infected CBA mice from the development of neurologic symptoms and acute death. In contrast, injection with an MAb directed against the Ly.2+ T cell subset had no protective effect. Second, thymectomized, irradiated, and bone marrow reconstituted (ATxBM) CBA mice did not develop acute cerebral malaria when infected by P. berghei, although parasitemia and anemia rose to the same extent as in normal P. berghei-infected CBA mice. The occurrence of lethal neurologic perturbations could be restored in ATxBM mice selectively reconstituted with L3T4+ Ly.2-lymphocytes but not with Ly.2+ L3T4- cells. Third, adoptive transfer of L3T4+ cells from mice dying of cerebral malaria into euthymic mice subsequently infected by P. berghei led to an acceleration of the disease. These results confirm that cerebral malaria in mice is the expression of immunopathologic reactions and outline the particular pathogenic importance of L3T4+ T cells. MH - Animal ; Antibodies, Monoclonal/DIAGNOSTIC USE ; Antigen-Antibody Complex/ ANALYSIS ; Antigens, Ly/IMMUNOLOGY ; Antigens, Protozoan/IMMUNOLOGY ; Antigens, Surface/IMMUNOLOGY ; Brain Diseases/*IMMUNOLOGY/PATHOLOGY ; Immunization, Passive ; Immunoglobulins/ANALYSIS ; Lymph Nodes/IMMUNOLOGY ; Malaria/*IMMUNOLOGY/PATHOLOGY ; Mice ; Plasmodium Berghei ; Support, Non-U.S. Gov't ; T Lymphocytes/*IMMUNOLOGY ; Thymectomy SO - J Immunol 1986 Oct 1;137(7):2348-54 9 UI - 87002591 AU - Fahey JR ; Spitalny GL TI - Immunity to Plasmodium yoelii: kinetics of the generation of T and B lymphocytes that passively transfer protective immunity against virulent challenge. AB - Adoptive immunization of A/Tru mice with splenic B cells or T cells from syngeneic donors with a primary, nonvirulent, Plasmodium yoelii (17X) infection confers on these recipients the capacity to resist a challenge infection with a virulent strain (YM) of P. yoelii. Unfractionated spleen cells as well as spleen cells enriched for T or B cells capable of transferring protective immunity were detected as early as Day 7 of the primary nonvirulent infection, and reached peak levels on Day 14. Spleen cells that were harvested from donor animals after resolution of the immunizing infection [on Days 21 or 28] were incapable of transferring protective immunity. The capacity of 7-day immune spleen cells to transfer immunity could be abolished by pretreatment with mitomycin C. In addition, it was found that immunocompetent recipient mice were required for successful adoptive immunization, since thymectomized, irradiated, bone marrow reconstituted mice infused with immune spleen cells failed to survive lethal challenge infections. MH - Animal ; B Lymphocytes/*IMMUNOLOGY ; Cell Division ; Female ; *Immunization, Passive ; Kinetics ; Malaria/*IMMUNOLOGY ; Mice ; Plasmodium/IMMUNOLOGY ; Spleen/IMMUNOLOGY ; Support, U.S. Gov't, P.H.S. ; T Lymphocytes/*IMMUNOLOGY SO - Cell Immunol 1986 Apr 1;98(2):486-95 10 UI - 86249525 AU - Theander TG ; Bygbjerg IC ; Jepsen S ; Svenson M ; Kharazmi A ; Larsen PB ; Bendtzen K TI - Proliferation induced by Plasmodium falciparum antigen and interleukin-2 production by lymphocytes isolated from malaria-immune individuals. AB - Affinity-purified Plasmodium falciparum soluble antigens (SPAg) isolated from in vitro cultures of the parasite were shown to be relatively free of nonspecific polyclonal activators. To determine the presence of lymphocytes with specificity against SPAg in the peripheral blood of malaria-immune individuals, the proliferative response and the interleukin-2 (IL-2) production of SPAg-activated mononuclear cells (MNCs) from individuals unexposed, sensitized, and immune to malaria were measured. It was found that MNC isolated from malaria-immune individuals proliferated in response to SPAg and that this activation resulted in measurable IL-2 production in 5 of 10 MNC cultures. MNC isolates from most unexposed individuals did not respond to SPAg. To establish which cells responded to SPAg, different subpopulations of MNCs were tested. Only T helper cells were found to respond, and they responded only when cocultured with monocytes. The finding of parasite-specific T helper cells in the blood of malaria-immune individuals and the fact that some of these cells were able to produce IL-2 in vitro support the hypothesis that in malaria the cellular part of the protective immune response is initiated by immune T cells. These cells may activate nonspecific effector cells (i.e., macrophages) that eliminate the parasite. MH - Adult ; Antigens, Protozoan/*IMMUNOLOGY ; Helper Cells/IMMUNOLOGY ; Human ; In Vitro ; Interleukin 2/*BIOSYNTHESIS ; Lectins/PHARMACODYNAMICS ; *Lymphocyte Transformation ; Malaria/*IMMUNOLOGY ; Plasmodium Falciparum/ *IMMUNOLOGY ; Support, Non-U.S. Gov't ; Suppressor Cells/IMMUNOLOGY ; T Lymphocytes/*IMMUNOLOGY SO - Infect Immun 1986 Jul;53(1):221-5 11 UI - 86225557 AU - Brake DA ; Weidanz WP ; Long CA TI - Antigen-specific, interleukin 2-propagated T lymphocytes confer resistance to a murine malarial parasite, Plasmodium chabaudi adami. AB - To explore cell-mediated immune mechanisms in host defense against malaria, we utilized a murine model system in which antibody-independent mechanisms of immunity are known to play a major role. Splenic T lymphocytes obtained from Plasmodium chabaudi adami-immune mice were maintained in vitro by using IL 2-containing medium and frequent antigenic stimulation. These IL 2-propagated T lymphocytes were characterized for their antigen reactivity, surface phenotype, and ability to confer protection to P. chabaudi adami in reconstituted mice. IL 2-dependent T lymphocytes maintained their capacity to proliferate in vitro to solubilized parasite preparations of homologous but not heterologous antigens. Antigen-specific proliferation was H-2 restricted, requiring antigen-presenting cells of the correct haplotype. More importantly, these propagated T lymphocytes were effective in adoptively transferring protection to both athymic nude mice and sublethally irradiated recipients. The protective response was dose dependent and antigen specific, because recipients resisted challenge infection with P. chabaudi adami but not with the heterologous parasite Plasmodium yoelii 17X. Pretreatment of the IL 2-propagated cells with anti-Thy-1.2 and complement abrogated their ability to transfer protection. Collectively, these results suggest that T lymphocytes obtained from P. chabaudi adami-immune mice, propagated and expanded in vitro, retain antigen specificity and passive protective activity in vivo. MH - Animal ; Antigenic Determinants/IMMUNOLOGY ; Antigens, Protozoan/ANALYSIS ; Dose-Response Relationship, Immunologic ; Female ; H-2 Antigens/ IMMUNOLOGY ; Immunity, Natural/RADIATION EFFECTS ; Immunization, Passive ; Immunologic Memory/RADIATION EFFECTS ; Interleukin 2/*PHYSIOLOGY ; *Lymphocyte Transformation/RADIATION EFFECTS ; Malaria/*IMMUNOLOGY ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred CBA ; Mice, Nude ; Phenotype ; Plasmodium/IMMUNOLOGY ; Radiation Chimera ; Support, U.S. Gov't, P.H.S. ; T Lymphocytes/*IMMUNOLOGY/TRANSPLANTATION SO - J Immunol 1986 Jul 1;137(1):347-52 12 UI - 86303028 AU - Maheshwari RK ; Czarniecki CW ; Dutta GP ; Puri SK ; Dhawan BN ; Friedman RM TI - Recombinant human gamma interferon inhibits simian malaria. AB - Prophylactic treatment with 0.1 mg of human gamma interferon per kg (body weight) per day completely suppressed experimental infection with Plasmodium cynomolgi B sporozoites in rhesus monkeys. Treatment with lower doses partially suppressed this infection. Prophylactic treatment with human gamma interferon, however, had no protective effect against trophozoite-induced infection, suggesting that the interferon effect was limited to the exoerythrocytic stage of parasitic development. MH - Animal ; Female ; Interferon Type II/*THERAPEUTIC USE ; Macaca mulatta ; Malaria/*PREVENTION & CONTROL ; Male ; Recombinant Proteins/THERAPEUTIC USE ; Support, U.S. Gov't, Non-P.H.S. ; Support, U.S. Gov't, P.H.S. SO - Infect Immun 1986 Sep;53(3):628-30 13 UI - 86269265 AU - Makonkawkeyoon S ; Kasinrerk W ; Vithayasai V TI - Regulation of immunoglobulin secretion by T lymphocytes in human malaria. AB - In vitro studies were carried out on the nature of immunoglobulin synthesis and secretion by peripheral blood mononuclear leukocytes (PBMLs) and on the function of T and B cells from malaria patients. The mean values of secreted IgG and IgM concentrations of 22 malaria patient PMBLs were significantly higher than those of 20 normal PBMLs. When the suppressor T cell activity and the function of B cells in response to suppressor T cells were assayed by the cell co-culture technique, it was found that there was a decrease in suppressor T cell activity and the B cell function in response to normal suppressor T cells in malaria patients. The defects of these T and B cell functions may play some role in the immunological abnormalities seen in some malaria patients. MH - Human ; IgG/BIOSYNTHESIS ; IgM/BIOSYNTHESIS ; Immunoglobulins/ *BIOSYNTHESIS ; In Vitro ; Malaria/*IMMUNOLOGY ; Pokeweed Mitogens/ PHARMACODYNAMICS ; Support, Non-U.S. Gov't ; Suppressor Cells/IMMUNOLOGY ; T Lymphocytes/*IMMUNOLOGY SO - Asian Pac J Allergy Immunol 1986 Jun;4(1):13-7 14 UI - 86261643 AU - Theander TG ; Bygbjerg IC ; Andersen BJ ; Jepsen S ; Kharazmi A ; Odum N TI - Suppression of parasite-specific response in Plasmodium falciparum malaria. A longitudinal study of blood mononuclear cell proliferation and subset composition. AB - The present longitudinal study was designed to characterize immunosuppression during acute Plasmodium falciparum infection, during the treatment and up to 1 month after the acute stage. The proliferative responses of blood mononuclear cells (BMNC) isolated from non-immune and semi-immune malaria patients and controls to mitogens and two Plasmodium-derived stimulators (merozoites, Meroz, and soluble purified antigen, SPag) and non-related antigens were measured by [3H]thymidine incorporation. BMNC isolated before treatment (day 0) from the non-immune patients did not respond to Meroz, whereas those from controls showed a significantly higher response. The SPag responses were also low in BMNC isolated on day 0 and increased in both the non-immune and the semi-immune patients during the observation period. These findings indicate that during malaria there is a depression of the parasite-specific proliferative response. The subset composition of BMNC isolated from non-immune patients was studied in a FACS analyser. The mean cell volumes of both Leu 2+ and Leu 3+ cells were increased during the acute phase of the infection, indicating that malaria infection results in activation of both T-helper and T-suppressor cells. There was no overall reduction of the response to mitogens on day 0. However, 3 days after initiation of the treatment the mitogen response was decreased. This finding indicates that it is important to distinguish between the effects of malaria infection and of drug treatment. MH - Antigenic Determinants/*IMMUNOLOGY ; Antigens, Protozoan/*IMMUNOLOGY ; Antigens, Surface/ANALYSIS ; Fluorescent Antibody Technic ; Human ; IgG/ ANALYSIS ; Longitudinal Studies ; *Lymphocyte Transformation ; Malaria/ *IMMUNOLOGY ; Mitogens/PHARMACODYNAMICS ; Phenotype ; Plasmodium Falciparum/IMMUNOLOGY ; Support, Non-U.S. Gov't ; Suppressor Cells/ CLASSIFICATION/*IMMUNOLOGY SO - Scand J Immunol 1986 Jul;24(1):73-81 15 UI - 86253098 AU - Good MF ; Berzofsky JA ; Maloy WL ; Hayashi Y ; Fujii N ; Hockmeyer WT ; Miller LH TI - Genetic control of the immune response in mice to a Plasmodium falciparum sporozoite vaccine. Widespread nonresponsiveness to single malaria T epitope in highly repetitive vaccine. AB - Different H-2 congenic strains of mice were immunized with a P. falciparum sporozoite vaccine currently being tested in humans, or with different segments of the vaccine molecule. Specific IgG production or lymph node cell proliferation in response to different antigens was then determined. Only four of seven strains (representing three of eight possible different class II restriction molecules) responded to the vaccine. Of those restriction molecules, only one, I-Ab, was associated with a response to a malaria-encoded T epitope [contained within NP(NANP)3NA], while the other two molecules (E alpha dE beta d and E alpha kE beta s) were associated with a T cell response to a nonmalarial epitope(s) carboxyterminal to the malaria sequence and encoded by a tetracycline resistance gene, read out of frame. If an analogous situation applies in humans, natural boosting by sporozoites will be very restricted. This has serious implications for the effectiveness of the vaccine, since constant high levels of antisporozoite antibodies and possibly antibody-independent T cell effector functions are required for immunity. MH - Animal ; Antibody Formation ; Antigenic Determinants/IMMUNOLOGY ; Antigens, Protozoan/*IMMUNOLOGY ; *Genes, Immune Response ; Immune Tolerance ; Lymphocyte Transformation ; Malaria/IMMUNOLOGY ; Mice ; Mice, Inbred C57BL ; Plasmodium Falciparum/GROWTH & DEVELOPMENT/*IMMUNOLOGY ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, Non-P.H.S. ; T Lymphocytes/ *IMMUNOLOGY ; Vaccines/*IMMUNOLOGY SO - J Exp Med 1986 Aug 1;164(2):655-60 16 UI - 86252250 AU - Chizzolini C ; Perrin L TI - Antigen-specific and MHC-restricted Plasmodium falciparum-induced human T lymphocyte clones. AB - We established and analyzed human T lymphocyte clones induced by crude Plasmodium falciparum antigens of schizont-enriched asexual blood stages. Peripheral blood mononuclear cells (PBMC) were stimulated for 6 days with antigen, and the T cell blasts were separated and were transferred to limiting dilution cultures with antigen, irradiated PBMC, and recombinant interleukin 2. The following observations were made. Malaria antigen (M.Ag) induced similar proportions of T blasts in PBMC from infected individuals and noninfected controls, and the M.Ag-dependent clone frequencies (1/79 to 1/216) obtained with the blasts were similar. The majority of established clones derived from infected and noninfected subjects specifically recognized M.Ag and would not proliferate in response to red blood cells or autologous PBMC alone. They also required HLA class II determinant-compatible antigen-presenting (E-) cells. With three clones from one malaria patient, DR 1 or DR 5 specificities correlated with antigen presentation. Although T4+ and T8+ blasts were induced by M.Ag in PBMC, only T4 (Leu-3+) clones were obtained in our culture system. These clones secreted IL 2 in response to M.Ag. 4) Differential patterns of reactivity to native M.Ag, heat-stable antigens, and heat-precipitated antigens were exhibited by T cell clones, and the tested clones did not recognize Plasmodium berghei antigen. In conclusion, it is important with regard to previous observations on apparently nonspecific, mitogen-like effects of M.Ag in bulk T cell cultures that our results demonstrate specific recognition of P. falciparum by human T cells. The T cell clones obtained will be an important tool in the quest for a better understanding of the mechanisms involved in resistance to malaria infection. MH - Adult ; Antigen-Presenting Cells/IMMUNOLOGY ; Antigenic Determinants/ *ANALYSIS ; Antigens, Protozoan/*IMMUNOLOGY ; Cell Communication ; Clone Cells/IMMUNOLOGY ; Human ; HLA Antigens/*IMMUNOLOGY ; *Lymphocyte Transformation ; Malaria/IMMUNOLOGY ; Plasmodium Falciparum/GENETICS/ *IMMUNOLOGY ; Support, Non-U.S. Gov't ; T Lymphocytes/*IMMUNOLOGY SO - J Immunol 1986 Aug 1;137(3):1022-8 17 UI - 86247984 AU - Van Zon AA ; Termaat RM ; Schetters TP ; Eling WM TI - Plasmodium berghei: reduction of the mouse's specific lymphoproliferative response in relation to corticosterone and pregnancy. AB - Spleen cells from mice immune to Plasmodium berghei exhibited a significantly increased in vitro proliferative response to parasitized reticulocytes compared to spleen cells from normal mice. The specific response to malaria antigen was decreased in spleen cells from pregnant immune mice in contrast to the nonspecific response to the mitogen phytohemagglutinin. Addition of mouse serum to spleen cell cultures of immune mice depressed both the phytohemagglutinin and the specific proliferative response, whereas serum of pregnant mice exerted an even stronger inhibition than serum of nonpregnant mice. Charcoal adsorption of mouse sera for the elimination of steroid hormones removed the serum dependent immunosuppression from normal as well as pregnant serum. Corticosterone added to the spleen cell cultures depressed also the proliferative response. These findings demonstrate that the response to malaria antigen is decreased in immune mice during pregnancy. The possible effect of serum corticosterone on the depression of the immune response is discussed. MH - Animal ; Antibody Formation/DRUG EFFECTS ; Corticosterone/ *PHARMACODYNAMICS ; Female ; Human ; Immune Tolerance/DRUG EFFECTS ; Immunity, Cellular/DRUG EFFECTS ; Malaria/*IMMUNOLOGY ; Mice ; Mice, Inbred Strains ; Plasmodium Berghei/IMMUNOLOGY ; Pregnancy ; Pregnancy Complications, Infectious/*IMMUNOLOGY/PARASITOLOGY ; Spleen/CYTOLOGY ; Support, Non-U.S. Gov't SO - Exp Parasitol 1986 Aug;62(1):71-8 18 UI - 86238832 AU - Bygbjerg IC ; Jepsen S ; Theander TG TI - Lymphocyte response to purified Plasmodium falciparum antigens during and after malaria. AB - The peripheral blood lymphocyte response to affinity purified soluble Plasmodium falciparum antigens from in vitro cultures was studied in seven patients with acute falciparum malaria, on eight occasions, and in 15 persons having had malaria, at various times post infection, on 24 occasions. During infection, the response was low or absent in most patients (median stimulating index = [SI] = 1.4). One week post infection, a specific antigen response rose (SI = 2.9), but not to the levels found two weeks to one year post infection (SI = 5.8). At two to four years post infection, it was still present. During a recrudescence of malaria in a single patient, it was lost temporarily. The response to optimal concentrations of lectin mitogens and to tuberculin antigen was not suppressed in acute malaria. MH - Adult ; Antigens, Protozoan/*IMMUNOLOGY/PHARMACODYNAMICS ; Concanavalin A/ PHARMACODYNAMICS ; Female ; Human ; *Lymphocyte Transformation ; Malaria/ *IMMUNOLOGY ; Male ; Phytohemagglutinins/PHARMACODYNAMICS ; Plasmodium Falciparum/*IMMUNOLOGY ; Pokeweed Mitogens/PHARMACODYNAMICS ; Support, Non-U.S. Gov't ; Time Factors ; Tuberculin/PHARMACODYNAMICS SO - Acta Trop (Basel) 1986 Mar;43(1):55-62 19 UI - 86222668 AU - Cavacini LA ; Long CA ; Weidanz WP TI - T-cell immunity in murine malaria: adoptive transfer of resistance to Plasmodium chabaudi adami in nude mice with splenic T cells. AB - Acute infections caused by the murine malarial parasite Plasmodium chabaudi adami are resolved by antibody-independent mechanisms of immunity. The fact that athymic nude mice developed high-grade unrelenting malaria and died when infected with this parasite suggested a significant role for T lymphocytes. Using adoptive transfer techniques, we demonstrated that spleen cells from either nonimmune or immune donor BALB/c mice eventually suppressed P. chabaudi adami infections in histocompatible recipient nude mice in a dose-dependent manner. Infections in recipients of "immune: spleen cells were less severe, demonstrating a depressed peak parasitemia and a shortened duration of patent infection, than was observed in recipients of normal spleen cells. Also, when sufficient numbers of immune spleen cells were transferred, the second wave of parasitemia (characteristic of this infection in nonimmune mice) failed to occur. T lymphocytes mediated protection in recipient mice, since T-cell-enriched, but not B-cell-enriched, spleen cell fractions suppressed P. chabaudi adami infections in nude mice. Protection was best achieved with T cells that bore the L3T4 phenotype. Patent parasitemias developed in all recipient mice, suggesting that the grafted cells did not limit parasite growth directly but achieved this end by activating other as yet unidentified inhibiting cell systems. MH - Animal ; Antibodies/IMMUNOLOGY ; Antigens, Surface/ANALYSIS ; Immunity, Cellular ; Immunization, Passive ; Malaria/*IMMUNOLOGY ; Mice ; Mice, Nude/IMMUNOLOGY ; Plasmodium/*IMMUNOLOGY ; Spleen/CYTOLOGY/IMMUNOLOGY ; Support, U.S. Gov't, P.H.S. ; T Lymphocytes/*IMMUNOLOGY SO - Infect Immun 1986 Jun;52(3):637-43 20 UI - 86208126 AU - Ferreira A ; Schofield L ; Enea V ; Schellekens H ; van der Meide P ; Collins WE ; Nussenzweig RS ; Nussenzweig V TI - Inhibition of development of exoerythrocytic forms of malaria parasites by gamma-interferon. AB - A specific DNA probe was used to study the effect of recombinant rat, mouse, and human gamma-interferon (gamma-IFN) on the course of sporozoite-induced malaria infections. In mice and rats infected with sporozoites of Plasmodium berghei, mouse and rat gamma-IFN's strongly inhibited the development of the exoerythrocytic forms in the liver liver cells of the hosts, but not the development of the erythrocytic stages. The degree of inhibition of the exoerythrocytic forms was proportional to the dose of gamma-IFN administered, but was independent of the number of sporozoites used for challenge. A 30 percent reduction in the development of exoerythrocytic forms in rat liver was achieved when 150 units (about 15 nanograms of protein) of rat gamma-IFN were injected a few hours before sporozoite challenge; the reduction was 90 percent or more with higher doses of gamma-IFN. The effect was less pronounced if the gamma-IFN was administered 18 hours before or a few hours after challenge. Human gamma-IFN also diminished the parasitemia in chimpanzees infected with sporozoites of the human malaria parasite Plasmodium vivax. The target of gamma-IFN activity may be the infected hepatocytes themselves, as shown by in vitro experiments in which small doses of the human lymphokine inhibited the development of exoerythrocytic forms of Plasmodium berghei in a human hepatoma cell line. These results suggest that immunologically induced interferon may be involved in controlling malaria infection under natural conditions. MH - Animal ; Cell Line ; Chimpansee troglodytes ; Human ; Interferon Type II/ PHARMACODYNAMICS/*THERAPEUTIC USE ; Liver/CYTOLOGY ; Malaria/*DRUG THERAPY ; Mice ; Plasmodium Berghei/DRUG EFFECTS ; Plasmodium Vivax/DRUG EFFECTS ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, Non-P.H.S. ; Toxoplasma/DRUG EFFECTS SO - Science 1986 May 16;232(4752):881-4 21 UI - 86207750 AU - Mori H ; Lenoir GM ; Franklin RM TI - Autoantibodies in Burkitt's lymphoma patients from the Ugandan prospective study. AB - Pre- and post syndrome sera from five Burkitt's lymphoma patients who partook in the Ugandan prospective study (A. Geser et al., Int. J. Cancer 29 (1982) 397-400) were investigated with respect to autoantibodies. Neighbours and siblings of these patients served as controls and all of these groups were compared with sera from 50 Caucasian normal controls (CNC). Antibody levels significantly higher than those in CNC were found in all African groups for actin, desmin, vimentin, tubulin, keratin, laminin, and collagen type I. Polyclonal B-cell activation, as measured by antibodies to DNP, and high levels of antibodies to P. falciparum were also found. Anti-DNP and antibodies to malaria were also present in sera from our earlier study on Burkitt's lymphoma (E. Vainio et al., Clin. exp. Immunol. 54 (1983) 387-396). Whereas EBV infected B cells do produce autoantibodies, there is a potentiation of autoantibody formation as a result of infection with malaria, which seems to provide an independent trigger of polyclonal B cell activation. This latter event might be one of the factors which results in a correlation of Burkitt's lymphoma with malaria endemic regions. MH - Adolescence ; Adult ; Animal ; Antibodies/ANALYSIS ; Autoantibodies/ *ANALYSIS ; B Lymphocytes/IMMUNOLOGY ; Burkitt's Lymphoma/ETIOLOGY/ *IMMUNOLOGY ; Child ; Child, Preschool ; Dinitrophenols/IMMUNOLOGY ; Erythrocytes/IMMUNOLOGY ; Human ; Lymphocyte Transformation ; Malaria/ COMPLICATIONS ; Middle Age ; Plasmodium Falciparum/IMMUNOLOGY ; Prospective Studies ; Serum Albumin, Bovine/IMMUNOLOGY ; Support, Non-U.S. Gov't ; Uganda SO - Trop Med Parasitol 1986 Mar;37(1):9-14 22 UI - 86162285 AU - Brown J ; Whittle HC ; Berzins K ; Howard RJ ; Marsh K ; Sjoberg K TI - Inhibition of Plasmodium falciparum growth by IgG antibody produced by human lymphocytes transformed with Epstein-Barr virus. AB - Supernatants from Epstein-Barr virus (EBV)--stimulated B lymphocytes obtained from two adult Gambians who were partially immune to malaria markedly inhibited the growth of Plasmodium falciparum in vitro (55-95% inhibition). When 22 separate colonies were derived by micromanipulation from one of these primary cultures and their supernatants assayed, the degree of inhibition correlated with levels of IgG fluorescent antibody and total IgG. The inhibitory anti-P. falciparum IgG immunoprecipitated an antigen of mol. wt 195,000, identified as the major schizont surface glycoprotein by dual biosynthetic labelling with 3H-glucosamine or 35S-methionine. Other studies on the analogous schizont surface protein of rodent malarias have shown that this antigen stimulates protective immunity. Production of this inhibitory antibody by adult Gambians may therefore contribute to their immunity to malaria. Human antibodies produced by EBV-stimulated B lymphocytes may be used to identify other important P. falciparum antigens and have potential applications for immunotherapy. MH - Adult ; Antibodies/*IMMUNOLOGY ; Antigens, Protozoan/IMMUNOLOGY ; B Lymphocytes/*IMMUNOLOGY ; Cells, Cultured ; Epstein-Barr Virus/IMMUNOLOGY ; Human ; IgG/*IMMUNOLOGY ; Lymphocyte Transformation ; Malaria/ IMMUNOLOGY ; Plasmodium Falciparum/GROWTH & DEVELOPMENT/*IMMUNOLOGY SO - Clin Exp Immunol 1986 Jan;63(1):135-40 23 UI - 86142023 AU - Ho M ; Webster HK ; Looareesuwan S ; Supanaranond W ; Phillips RE ; Chanthavanich P ; Warrell DA TI - Antigen-specific immunosuppression in human malaria due to Plasmodium falciparum. AB - Proliferative responses of T lymphocytes to antigens specific and not specific for malaria were investigated in 32 adult patients in eastern Thailand during acute infection with Plasmodium falciparum malaria and during their convalescence. Immune unresponsiveness to malarial antigen, which persisted for more than four weeks in 37.5% of the individuals, was present in all patients, irrespective of parasitemia or severity of clinical illness. Suppression of responses to nonspecific antigens was less profound and observed only in patients with moderately severe or cerebral malaria. The depressed functional responses were associated with a loss of T lymphocytes--both helper and suppressor subsets--from the peripheral blood; these responses were recovered once parasites were cleared. These results indicate that blood-stage plasmodial infections may suppress responses important for immunity to malaria and so allow the parasite to survive. They further suggest that patients acutely or even recently infected with P. falciparum may not respond as well to a malaria vaccine as would uninfected individuals. MH - Adolescence ; Adult ; Antibodies/ANALYSIS ; Antigens, Protozoan/ *IMMUNOLOGY ; Brain Diseases/ETIOLOGY/IMMUNOLOGY ; Female ; Helper Cells/ IMMUNOLOGY ; Human ; *Immune Tolerance ; Leukocyte Count ; Lymphocyte Transformation ; Malaria/*IMMUNOLOGY ; Male ; Middle Age ; Plasmodium Falciparum/*IMMUNOLOGY ; Support, Non-U.S. Gov't ; Suppressor Cells/ IMMUNOLOGY SO - J Infect Dis 1986 Apr;153(4):763-71 24 UI - 86127922 AU - Collins DP ; Deas JE TI - The effects of cortisone on immunity during chronic rodent malaria. AB - The temporal effects were studied of a single dose of hydrocortisone acetate on the development and expression of immune responses to Plasmodium berghei in mice with chronic infections. Cortisone administration prior to primary infection reduced malaria-specific secondary humoral and cellular responses, as well as the ability to survive parasite challenge. Once protective humoral immunity was established after chemotherapy of primary infection, cortisone treatment did not disrupt its expression. Administration of cortisone during subpatent chronic infection resulted in a transient recrudescence of parasitemia not apparent in untreated mice. Clearance of recrudescence or parasite challenge was associated with a rapid cortisone-resistant antibody response. During subpatent chronic infection, malaria-specific antibody levels were reduced, whereas delayed-type hypersensitivity (DTH) to malaria antigens and heterologous antigens was well developed. At least two systems of immunity to malaria appear to be present during chronic infection. Recrudescence of parasitemia may be prevented by antibody-independent, cortisone-sensitive cellular immunity. Once parasitemia becomes overt after cortisone treatment, or parasites are reintroduced with challenge, cortisone-resistant humoral immunity appears to mediate parasite clearance. Regulation of these systems may be a dose-dependent phenomenon which results in the persistence of parasites, albeit at subpatent levels. MH - Animal ; Antigens, Protozoan/IMMUNOLOGY ; Chronic Disease ; Female ; Hydrocortisone/*ANALOGS & DERIVATIVES/PHARMACODYNAMICS ; Hypersensitivity, Delayed/IMMUNOLOGY ; Immunity/*DRUG EFFECTS ; Immunity, Cellular/DRUG EFFECTS ; Malaria/DRUG THERAPY/*IMMUNOLOGY ; Mice ; Plasmodium Berghei ; Sulfadiazine/THERAPEUTIC USE ; Support, Non-U.S. Gov't ; Time Factors SO - Am J Trop Med Hyg 1986 Jan;35(1):16-21 25 UI - 86080229 AU - Stach JL ; Dufrenoy E ; Roffi J ; Bach MA TI - T-cell subsets and natural killer activity in Plasmodium falciparum-infected children. AB - Thirty children acutely infected by Plasmodium falciparum and suffering either benign uncomplicated malaria (17 cases), or cerebral malaria (13 cases), were investigated for T-cell number and subset distribution among peripheral blood mononuclear cells using OKT3, OKT4, and OKT8 monoclonal antibodies, and for natural killer (NK) activity using K562 cells as targets. They were compared to a group of 16 age- and sex-matched healthy Senegalese children. OKT8 cell percentage was found increased in both groups of patients with a decrease of OKT4 cell percentage in cerebral malaria patients only. Both groups thus exhibited a decreased OKT4/OKT8 ratio, which was slightly lower in cerebral malaria cases than in benign cases. NK activity was found elevated in uncomplicated cases of malaria, in contrast to patients suffering cerebral malaria, who exhibited a profound depression of NK activity. MH - Adolescence ; Brain Diseases/IMMUNOLOGY ; Child ; Child, Preschool ; Human ; Killer Cells, Natural/*IMMUNOLOGY ; Malaria/*IMMUNOLOGY ; Plasmodium Falciparum ; T Lymphocytes/*CLASSIFICATION SO - Clin Immunol Immunopathol 1986 Jan;38(1):129-34