==================================BSR35================================== 35. I am interested in research on cytotoxic T lymphocytes (sometimes called killer T cells) in diseases of the liver. I am interested in any disease, but I suggest that particularly viral hepatitis and halothane hepatitis may be the best studies in terms of these cells. 1 UI - 87108091 AU - Mondelli MU ; Alberti A ; Realdi G ; Rondanelli EG TI - In vitro effect of lymphoblastoid alpha-interferon on subpopulations of effector cells mediating cytotoxicity for autologous hepatocytes in hepatitis B and non-A, non-B. AB - Controlled clinical trials are currently under way to assess the efficacy of interferon (IFN) in hepatitis B virus (HBV) infection. In the present study, T-enriched and non-T-enriched lymphocytes from six patients with acute and six patients with chronic HBV infection were cocultured with autologous liver cells with and without alpha-IFN (lymphoblastoid) at a concentration of 1000 U/ml of culture medium, in an 18 h cytotoxicity assay. IFN produced a significant enhancement of non-T-cell cytotoxicity in patients with acute and chronic HBV infection, from 34.3 +/- 19.6% to 60.0 +/- 11.2%, P less than 0.03, and from 41.2 +/- 17.2% to 65.5 +/- 9.8%, P less than 0.01, respectively. In contrast, no significant effect was observed on T cell-mediated cytotoxicity in either group of patients. The in vitro effect of alpha-IFN was also evaluated in four patients who developed chronic non-A, non-B hepatitis following blood transfusion, but no significant stimulatory effect was noted on either T- or non-T cell cytotoxicity. Similarly, no significant increase was observed in control subjects. The significant enhancement of non-T cell cytotoxicity, but not of T-cell cytotoxicity, for autologous hepatocytes in HBV infection suggests that alpha-IFN produces a selective stimulatory effect on non-T cells. The absence of a similar effect in patients with chronic non-A, non-B hepatitis and control subjects suggests that HBV infection alters the susceptibility of hepatocytes to IFN-stimulated non-T cell damage. MH - Adolescence ; Adult ; Child ; Cytotoxicity, Immunologic ; Female ; Hepatitis B/*IMMUNOLOGY/THERAPY ; Hepatitis, Viral, Human/*IMMUNOLOGY ; Hepatitis, Viral, Non-A, Non-B/*IMMUNOLOGY/THERAPY ; Human ; Immunotherapy ; In Vitro ; Interferon Type I/*PHARMACODYNAMICS ; Killer Cells, Natural/IMMUNOLOGY ; Liver/IMMUNOLOGY ; Male ; Middle Age ; Support, Non-U.S. Gov't ; T Lymphocytes, Cytotoxic/IMMUNOLOGY SO - Int J Immunopharmacol 1986;8(8):887-91 2 UI - 87081794 AU - Vallbracht A ; Gabriel P ; Maier K ; Hartmann F ; Steinhardt HJ ; M:uller C ; Wolf A ; Manncke KH ; Flehmig B TI - Cell-mediated cytotoxicity in hepatitis A virus infection. AB - We studied cell-mediated cytotoxicity to hepatitis A virus-infected cells in seven patients with acute type A hepatitis and two controls. Skin fibroblast cultures obtained from the skin biopsies of seven patients after acute hepatitis A virus infection and from two persons without history of current or past hepatitis A virus infection were inoculated with hepatitis A virus. Infection of fibroblast cultures always resulted in an inapparent, persistent infection with production and release of infectious hepatitis A virus. Peripheral blood lymphocytes were collected from the same patients at different times after onset of icterus and were stored in liquid nitrogen. Cytolytic activity of peripheral blood lymphocytes was determined by a microcytotoxicity assay using autologous 51Cr-labeled hepatitis A virus-infected and uninfected target cells. Cytotoxic peripheral blood lymphocytes capable of lysing autologous hepatitis A virus-infected skin fibroblasts were detected in all patients with hepatitis A but were not demonstrable in the controls without antibodies against hepatitis A virus. The clinical course of the hepatitis A virus infection was normal in five patients; and in these patients, cytolytic activity of peripheral blood lymphocytes against hepatitis A virus-infected autologous targets peaked 2 to 3 weeks after onset of icterus. A clinically protracted form of the disease with persistent elevation of aminotransferases for at least 5 months after onset was present in two patients. In these cases, the highest cytolytic activity was demonstrated in peripheral blood lymphocytes collected 8 to 12 weeks after onset of icterus.(ABSTRACT TRUNCATED AT 250 WORDS) MH - Acute Disease ; Adolescence ; Adult ; Cytotoxicity Tests, Immunologic ; *Cytotoxicity, Immunologic ; Female ; Fibroblasts ; Hepatitis A Virus/ IMMUNOLOGY ; Hepatitis A/*IMMUNOLOGY ; Hepatitis Antibodies/ANALYSIS ; Human ; Male ; Support, Non-U.S. Gov't ; T Lymphocytes, Cytotoxic/ IMMUNOLOGY SO - Hepatology 1986 Nov-Dec;6(6):1308-14 3 UI - 87010413 AU - Zinkernagel RM ; Haenseler E ; Leist T ; Cerny A ; Hengartner H ; Althage A TI - T cell-mediated hepatitis in mice infected with lymphocytic choriomeningitis virus. Liver cell destruction by H-2 class I-restricted virus-specific cytotoxic T cells as a physiological correlate of the 51Cr-release assay? AB - A model for immunologically T cell-mediated hepatitis was established in mice infected with lymphocytic choriomeningitis virus (LCMV). The severity of hepatitis was monitored histologically and by determination of changes in serum levels of the enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), and alkaline phosphatase (AP). Kinetics of histological disease manifestations, increases of liver enzyme levels in the serum, and cytotoxic T cell activities in livers and spleens all correlated and were dependent upon several parameters: LCMV-isolate; LCMV-WE caused extensive hepatitis, LCMV-Armstrong virtually none. Virus dose. Route of infection; i.v. or i.p. infection caused hepatitis, whereas infection into the footpad did not. The general genetic background of the murine host; of the strains tested, Swiss mice and A-strain mice were more susceptible than C57BL or CBA mice; BALB/c and DBA/2 mice were least susceptible. The degree of immunocompetence of the murine host; T cell deficient nu/nu mice never developed hepatitis, whereas nu/+ or +/+ mice always did. B cell-depleted anti-IgM-treated mice developed immune-mediated hepatitis comparably or even more extensively than control mice. Local cytotoxic T cell activity; mononuclear cells isolated from livers during the period of overt hepatitis were two to five times more active than equal numbers of spleen cells. Adoptive transfer of nylon wool-nonadherent anti-Thy-1.2 and anti-Lyt-2 plus C-sensitive, anti-L3T4 plus C-resistant lymphocytes into irradiated mice preinfected with LCMV-WE caused a rapid time- and dose-dependent linear increase of serum enzyme levels. This increase was caused by adoptive transfer of lymphocytes if immune cell donors and recipient mice shared class I, but not when they shared class II histocompatibility antigens. The donor cell dose-dependent increase of these enzymes was first measurable 6-18 h after transfer with 2 X 10(8) cells or 3 X 10(6) cells, respectively. The time-dependent increase caused by the adoptive transfer of 1-2 X 10(8) cells was strictly linear during a period of up to 25-40 h. These results indicate single-hit kinetics of liver cell death and suggest that effector T cells destroy infected liver cells via direct contact rather than via soluble toxic mediators. The results may represent the best in vivo correlate of the in vitro 51Cr-release assay that has been analyzed so far, and strongly support the view that antiviral cytotoxic T cells are directly cytolytic in vivo.(ABSTRACT TRUNCATED AT 400 WORDS) MH - Alanine Aminotransferase/BLOOD ; Animal ; Aspartate Aminotransferase/ BLOOD ; Chromium Radioisotopes/DIAGNOSTIC USE ; Cytotoxicity Tests, Immunologic ; Female ; Glutamate Dehydrogenase/BLOOD ; H-2 Antigens/ *IMMUNOLOGY ; Hepatitis B/IMMUNOLOGY ; Hepatitis, Viral, Animal/*ETIOLOGY ; IgM/IMMUNOLOGY ; Immunization, Passive ; Liver/IMMUNOLOGY/*PATHOLOGY ; Lymphocytic Choriomeningitis/*IMMUNOLOGY/PATHOLOGY ; Male ; Mice ; Mice, Inbred Strains ; Species Specificity ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S. ; T Lymphocytes, Cytotoxic/*IMMUNOLOGY SO - J Exp Med 1986 Oct 1;164(4):1075-92 4 UI - 87006880 AU - Nakajima T ; Mizushima N ; Nakamura J ; Kanai K TI - Surface markers of NK cells in peripheral blood of patients with cirrhosis and hepatocellular carcinoma. AB - The surface markers and NK activity of blood lymphocytes in 38 normal controls, 57 cirrhotic patients and 22 cirrhotics with hepatocellular carcinoma were studied by the flow cytofluorometry using monoclonal antibodies. A reduction of OKM1+ cells was remarkable in cirrhotics, and a further decrease in HNK-1+ cells as well as OKM1+ cells was observed in cirrhotics with hepatocellular carcinoma, accompanied by depression of NK activity. We postulate that the decreased NK activity in these patients may result from the disturbed maturation of NK cells. MH - Aged ; Antibodies, Monoclonal/DIAGNOSTIC USE ; Antigens, Surface/ *ANALYSIS/IMMUNOLOGY ; Cell Separation ; Cytotoxicity, Immunologic ; Female ; Flow Cytometry/METHODS ; Helper Cells/IMMUNOLOGY ; Hepatoma/ *BLOOD ; Human ; Killer Cells, Natural/IMMUNOLOGY/*ULTRASTRUCTURE ; Liver Cirrhosis/*BLOOD ; Liver Neoplasms/*BLOOD ; Male ; Middle Age ; T Lymphocytes, Cytotoxic/IMMUNOLOGY SO - Immunol Lett 1986 Aug;13(1-2):7-10 5 UI - 86298231 AU - Hakim AA ; Siraki CM TI - Plasma "cold-insoluble globulin: protects cytotoxic lymphocytes from ATP inhibition: 2. Immunization against viral cell surface antigen stimulates cytotoxic cells to lyse tumor cells. AB - The present studies examined the immunoregulatory factors that modulate T-lymphocyte cytotoxic activity against tumor cells. At 30 days postvaccination with hepatitis B virus surface antigen(s) (HBsAg), peripheral blood lymphocytes (PBL) from HBsAb-seropositive healthy donors showed 8-10-fold increase in their cytotoxic activity against human hepatocellular carcinoma PLC/PRF/5 cells. However, there was no effect against human embryonic liver or lung fibroblasts (WI-35) cells. After cloning, these cytotoxic lymphocytes responded to HBsAg, phytohemagglutinin (PHA), and neuraminidase (VCN) with significant increases in cytotoxicity. These cloned, activated PBL also had no effect on human embryonic liver or lung fibroblasts. Exogenous 5'-triphosphate (ATP) inhibited the lymphocyte cytotoxic activities. The inhibition was ATP concentration-dependent. Also, colchicine, a tubuline depolymerizing agent, inhibited effector cell cytotoxic lymphocyte activity. Colchicine binds to the target cells without causing cell lysis. Preincubation of the cytotoxic lymphocytes with "cold-insoluble globulin: (CIg) protected the cells from ATP and colchicine inhibition. MH - Adenosine Triphosphate/*PHARMACODYNAMICS ; Antibodies, Monoclonal/ DIAGNOSTIC USE ; Cell Line ; Cytotoxicity Tests, Immunologic ; Fibronectins/*IMMUNOLOGY ; Hepatitis B Surface Antigens/*IMMUNOLOGY ; Hepatoma/IMMUNOLOGY ; Human ; Immunization ; Interleukin 2/IMMUNOLOGY ; Liver Neoplasms/IMMUNOLOGY ; Neoplasms/*IMMUNOLOGY ; T Lymphocytes, Cytotoxic/*IMMUNOLOGY SO - Cancer Detect Prev 1986;9(3-4):373-83 6 UI - 86280922 AU - Pignata C ; Vajro P ; Monaco G ; Fontanella A TI - Immunoregulatory functional abnormalities in children affected by HBsAg-positive chronic active hepatitis: role of prostaglandins in T-mediated suppression. AB - Suppressor cell function was evaluated in children affected by HBsAg-positive chronic active hepatitis. Circulating concanavalin A- (ConA) precultured lymphocytes failed to suppress the proliferative response of autologous responder cells to a mitogen. In four of eight patients with a failure of ConA-induced suppressor activity, indomethacin added during the induction phase of T suppressor cells abolished the defect, indicating that prostaglandin-producing adherent cells may influence ConA-induced suppressor activity. An inverse relationship between suppressor cell activity and the number of suppressor/cytotoxic subsets defined by the OK T8 monoclonal antibody was found. Our findings strongly support the hypothesis that an abnormality in the immunoregulatory system plays a role in the pathogenesis of HBsAg-related chronic active hepatitis. It is also suggested that non-T regulatory cells are implicated in the immunological abnormality in chronic active hepatitis. MH - Adolescence ; Antibodies, Monoclonal/DIAGNOSTIC USE ; Cells, Cultured ; Child ; Child, Preschool ; Concanavalin A/PHARMACODYNAMICS ; Hepatitis B Surface Antigens/*ANALYSIS ; Hepatitis, Chronic Active/*IMMUNOLOGY ; Human ; Indomethacin/PHARMACODYNAMICS ; Mitogens/PHARMACODYNAMICS ; Prostaglandins/*PHYSIOLOGY ; Suppressor Cells/DRUG EFFECTS/*IMMUNOLOGY ; T Lymphocytes/CLASSIFICATION ; T Lymphocytes, Cytotoxic/IMMUNOLOGY SO - J Pediatr Gastroenterol Nutr 1986 Jul-Aug;5(4):537-41 7 UI - 86245763 AU - Stefanini GF ; Mazzetti M ; Zunarelli P ; Baraldini M ; Pignatelli M ; Canonica GW ; Miglio F ; Gasbarrini G TI - T lymphocyte subsets implicated in cytotoxicity in autologous hepatocytes in chronic active hepatitis patients with active viral replication. AB - We investigated inhibitory effect of various monoclonal antibodies on T-cell-mediated cytotoxicity against autologous hepatocytes in 24 patients with hepatitis B surface antigen/hepatitis B e antigen (HBsAg/HBeAg)-positive chronic active hepatitis. A significant reduction of cytotoxicity index occurred after preincubation of T lymphocytes with anti-Leu 7 (killer-natural killer cells), D1/12 (Ia-positive cells), 5/9 (restricted helper/inducer cells), and MLR4 ("activated: and radiosensitive helper cells) monoclonal antibodies (MAb). Anti-Leu 2a (cytotoxic/suppressor cells) and anti-Leu 3a (helper/inducer cells) MAb did not affect cytotoxic activity. This finding supports the hypothesis that the T cytotoxic reaction in this in vitro system is probably due to two mechanisms: first, spontaneous cell membrane cytotoxicity sustained by anti-Leu-7-positive lymphocytes; and second, specific cytotoxicity mediated by activated Ia-positive cells. We also found that the presence of helper/inducer cells (5/9 positive) appears to be a prerequisite for the cytotoxic reaction. MH - Adult ; Antibodies, Monoclonal/IMMUNOLOGY ; Cytotoxicity, Immunologic ; DNA Replication ; Female ; Hepatitis B/*IMMUNOLOGY ; Hepatitis B Virus/ IMMUNOLOGY/PHYSIOLOGY ; Hepatitis, Chronic Active/*IMMUNOLOGY ; Human ; Liver/*IMMUNOLOGY ; Male ; Middle Age ; Support, Non-U.S. Gov't ; T Lymphocytes, Cytotoxic/*CLASSIFICATION ; Virus Replication SO - Clin Immunol Immunopathol 1986 Aug;40(2):214-23 8 UI - 86229834 AU - Barnaba V ; Levrero M ; Franco A ; Ruberti G ; Musca A ; Bonavita MS ; Balsano F TI - Characterization of effector cells in lymphocytotoxicity to autologous hepatocytes in HBsAg-positive and autoimmune chronic active hepatitis (CAH). AB - Peripheral blood lymphocyte subsets involved in cytotoxicity to autologous hepatocytes have been characterized by isolation on antibody-coated Petri dishes in autoimmune and HBsAg-positive chronic active hepatitis (CAH). In autoimmune CAH and in HBsAg-positive CAH without HBcAg in liver tissue, cytotoxicity is sustained by non-T lymphocytes and is confined to M1-positive cells bearing Fc receptors: M1 cytotoxicity inhibition by adding aggregated IgG suggests that these cells are responsible for an antibody-dependent cell-mediated mechanism (ADCC). Moreover, when T-enriched fractions were separated in T4, T8 and 5/9 positive subsets, only the first one showed a significant cytotoxicity: T4 positive cells might act as cytotoxic T cells or might be involved in delayed type hypersensitivity (DTH) reactions. Cytotoxic T lymphocytes in HBsAg-positive CAH with HBcAg in liver tissue are confined in T8 positive subset, while helper/inducer T cells (T4 positive or 5/9 positive) seem to play an important role only in the induction of cell-mediated injury against hepatocytes. The inhibition of T cell-cytotoxicity by preincubating liver cells with monoclonal antibody (Mab) anti-HLA AB and not with Mab anti-HLA DR or aggregated IgG supports the involvement of the class I major histocompatibility complex (MHC) expressed on the hepatocyte surface. MH - Antibodies, Monoclonal/IMMUNOLOGY ; Antigens, Immune Response/IMMUNOLOGY ; Autoimmune Diseases/*IMMUNOLOGY ; Cytotoxicity, Immunologic ; Female ; Hepatitis B/*IMMUNOLOGY ; Hepatitis B Surface Antigens/ANALYSIS ; Hepatitis, Chronic Active/*IMMUNOLOGY ; Human ; Hypersensitivity, Delayed/ IMMUNOLOGY ; HLA Antigens/IMMUNOLOGY ; IgG/IMMUNOLOGY ; Liver/IMMUNOLOGY/ PATHOLOGY ; Receptors, Fc/IMMUNOLOGY ; T Lymphocytes/CLASSIFICATION/ IMMUNOLOGY ; T Lymphocytes, Cytotoxic/*IMMUNOLOGY SO - Liver 1986 Feb;6(1):45-52 9 UI - 86107705 AU - Jovanovic R ; Worner T ; Lieber CS ; Paronetto F TI - Lymphocyte subpopulations in patients with alcoholic liver disease. AB - To determine whether abnormalities of the lymphocyte populations are associated with alcoholic liver disease, we have characterized the subpopulations of lymphocytes in 30 alcoholic patients with and without liver disease. Total T lymphocytes were decreased in patients with alcoholic hepatitis and alcoholic cirrhosis. However, T4 (helper) and T8 (suppressor/cytotoxic) cells and the T4 and T8 cell ratio were similar to the values in controls. In these patients, the sums of T4/T8 cells exceeded that of total T cells, an alteration apparently related to severe liver damage. Cells reacting with antisera to immunoglobulins (B lymphocytes) and to Dr determinants were also within the normal range. In contrast, NK/K (natural killer/killer) cells were increased in the group of patients with steatosis or without liver alteration. Increase of NK/K cells was not observed in patients who were abstinent from alcohol for a period of two weeks or more, suggesting that alcohol may have been responsible for the increase in this lymphocyte population. MH - Adult ; Aged ; Antibodies, Monoclonal/DIAGNOSTIC USE ; Antigenic Determinants/IMMUNOLOGY ; Antigens, Immune Response/IMMUNOLOGY ; Comparative Study ; Female ; Fluorescent Antibody Technic ; Helper Cells/ CLASSIFICATION ; Human ; Immunoglobulins, Surface/IMMUNOLOGY ; Killer Cells/CLASSIFICATION ; Killer Cells, Natural/CLASSIFICATION ; Liver Diseases, Alcoholic/BLOOD/*IMMUNOLOGY ; Lymphocytes/*CLASSIFICATION ; Male ; Middle Age ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, Non-P.H.S. ; Support, U.S. Gov't, P.H.S. ; Suppressor Cells/ CLASSIFICATION ; T Lymphocytes/CLASSIFICATION ; T Lymphocytes, Cytotoxic/ CLASSIFICATION SO - Dig Dis Sci 1986 Feb;31(2):125-30 10 UI - 86222190 AU - Yamada G ; Hyodo I ; Tobe K ; Mizuno M ; Nishihara T ; Kobayashi T ; Nagashima H TI - Ultrastructural immunocytochemical analysis of lymphocytes infiltrating bile duct epithelia in primary biliary cirrhosis. AB - Subpopulations of lymphocytes in portal areas, especially infiltrating bile duct epithelia were analyzed by light and electron microscopy using indirect peroxidase-labeled antibody method and monoclonal antibodies against pan-T (Leu 1), cytotoxic/suppressor T (Leu 2a), helper/inducer T (Leu 3a) and natural killer/K (Leu 7) and suppressor T (Leu 15) cells in liver biopsy specimens from four patients with primary biliary cirrhosis. Bile ducts with chronic nonsuppurative destructive cholangitis were observed in two patients. Leu 1+ and Leu 2+ cells were frequently seen in intimate contact with epithelial ductal cells. The majority of intraepithelial cells possessing Leu 2a antigen did not react with anti-Leu 15 antibody. Leu 3a+ or Leu 7+ cells seldom infiltrated ductal epithelia. These findings indicate that the majority of intraepithelial lymphocytes in bile ducts most likely represent Leu 2a+15- cytotoxic T cells. By immunoelectron microscopy, Leu 1+ or Leu 2a+ lymphocytes often breached the basement membrane of bile ducts and were present within dilated intercellular spaces between biliary epithelial cells. Furthermore, they often formed sharp or broad contacts with the epithelial cells, and occasionally pseudopods projecting from the surfaces of Leu 2a+ cells extended into the epithelial cells. Most of Leu 2a+ lymphocytes contained little cytoplasm with few granules and a small Golgi apparatus. Such findings suggest that cytotoxic T cells may contribute to the pathogenesis of chronic nonsuppurative destructive cholangitis in primary biliary cirrhosis. MH - Adult ; Antibodies, Monoclonal/IMMUNOLOGY ; Antigens, Surface/IMMUNOLOGY ; Bile Ducts, Intrahepatic/CYTOLOGY ; Cholangitis/PATHOLOGY ; Epithelium/ CYTOLOGY ; Female ; Helper Cells/IMMUNOLOGY ; Human ; Killer Cells, Natural/IMMUNOLOGY ; Liver Cirrhosis, Biliary/*IMMUNOLOGY ; Male ; Microscopy, Electron ; Middle Age ; Support, Non-U.S. Gov't ; Suppressor Cells/IMMUNOLOGY ; T Lymphocytes/*IMMUNOLOGY/ULTRASTRUCTURE ; T Lymphocytes, Cytotoxic/IMMUNOLOGY SO - Hepatology 1986 May-Jun;6(3):385-91 11 UI - 86162287 AU - Mondelli M ; Alberti A ; Tremolada F ; Williams R ; Eddleston AL ; Realdi G TI - In-vitro cell-mediated cytotoxicity for autologous liver cells in chronic non-A, non-B hepatitis. AB - To investigate the possible mechanisms of liver cell injury in chronic non-A, non-B (NANB) hepatitis, peripheral blood lymphocytes (PBL) from 16 patients with chronic NANB hepatitis were incubated with autologous hepatocytes in a microcytotoxicity assay. Significant cytotoxicity was demonstrated in 11 patients. T-enriched lymphocytes exhibited significantly greater cytotoxicity than non-T enriched cells. No significant inhibition of cytotoxicity was observed following preincubation of the liver cells with either monoclonal or polyclonal anti-HBc, or monoclonal anti-HBs, or addition of either purified HBsAg or recombinant HBcAg to the culture, indicating that there was no detectable cross-reactivity in this system between hepatitis B virus (HBV) and NANB-associated antigen(s). Preincubation of the patients' hepatocytes with polyclonal IgG purified from a serum of a patient who recovered from an acute NANB hepatitis, did not significantly alter cytotoxicity. Liver cell surface-bound IgG was detected by immunofluorescence in only two of the patients, a finding consistent with existing evidence of poor antibody responses to both liver membrane and NANB-associated antigens. Control experiments using PBL from allogeneic normal donors exhibited normal cytotoxicity for the patients' hepatocytes supporting the hypothesis that antibody-dependent cell-mediated cytotoxicity (ADCC) is unlikely to play a significant role in this clinical setting. MH - Adolescence ; Adult ; Aged ; Cells, Cultured ; Child ; *Cytotoxicity, Immunologic ; Female ; Hepatitis Antibodies/IMMUNOLOGY ; Hepatitis, Viral, Human/*IMMUNOLOGY ; Hepatitis, Viral, Non-A, Non-B/*IMMUNOLOGY ; Human ; IgG/IMMUNOLOGY ; Liver/*IMMUNOLOGY ; Lymphocytes/*IMMUNOLOGY ; Male ; Middle Age ; Support, Non-U.S. Gov't ; T Lymphocytes, Cytotoxic/ IMMUNOLOGY SO - Clin Exp Immunol 1986 Jan;63(1):147-55 12 UI - 86141890 AU - Fujiwara H ; Yoshioka T ; Shima J ; Kosugi A ; Itoh K ; Hamaoka T TI - Helper T cells against tumor-associated antigens (TAA): preferential induction of helper T cell activities involved in anti-TAA cytotoxic T lymphocyte and antibody responses. AB - This study establishes assay systems for helper T cell activities assisting cytotoxic T lymphocyte (CTL) and antibody responses to tumor-associated antigens (TAA) and demonstrates the existence of TAA that induce preferentially anti-TAA CTL helper and B cell helper T cell activities in two syngeneic tumor models. C3H/HeN mice were immunized to the syngeneic X5563 plasmacytoma or MH134 hepatoma. Spleen cells from these mice were tested for anti-TAA helper T cell activity capable of augmenting anti-trinitrophenyl(TNP) CTL and anti-TNP antibody responses from anti-TNP CTL and B cell precursors (responding cells) by stimulation with TNP-modified X5563 or MH134 tumor cells. The results demonstrate that cultures of responding cells plus 85OR X-irradiated tumor-immunized spleen cells (helper cells) failed to enhance anti-TNP CTL or antibody responses when in vitro stimulation was provided by either unmodified tumor cells or TNP-modified syngeneic spleen cells (TNP-self). In contrast, these cultures resulted in appreciable augmentation of anti-TNP CTL or antibody response when stimulated by TNP-modified tumor cells. Such anti-TAA helper activities were revealed to be Lyt-1+2- T cell mediated and TAA specific. Most interestingly, immunization with X5563 tumor cells resulted in anti-TAA helper T cell activity involved in CTL, but not in antibody responses. Conversely, TAA of MH134 tumor cells induced selective generation of anti-TAA helper T cell activity responsible for antibody response. These results indicate that there exists the qualitative TAA-heterogeneity as evidenced by the preferential induction of anti-TAA CTL- and B cell-helper T cell activities. The results are discussed in the light of cellular mechanisms underlying the preferential anti-TAA immune responses, and the interrelationship between various types of cell functions including CTL- and B cell-help. MH - Animal ; Antibodies, Neoplasm/*BIOSYNTHESIS ; Antigens, Neoplasm/ *IMMUNOLOGY ; B Lymphocytes/IMMUNOLOGY ; Cell Line ; *Cytotoxicity, Immunologic ; Female ; Growth Substances/BIOSYNTHESIS ; Helper Cells/ *IMMUNOLOGY/METABOLISM ; Hepatoma/IMMUNOLOGY ; Liver Neoplasms/IMMUNOLOGY ; Lymphokines/BIOSYNTHESIS ; Mice ; Mice, Inbred C3H ; Plasmacytoma/ IMMUNOLOGY ; Support, Non-U.S. Gov't ; T Lymphocytes, Cytotoxic/ *IMMUNOLOGY SO - J Immunol 1986 Apr 1;136(7):2715-9 13 UI - 86056781 AU - Duffy LF ; Daum F ; Kahn E ; Teichberg S ; Pahwa R ; Fagin J ; Kenigsberg K ; Kaplan M ; Fisher SE ; Pahwa S TI - Hepatitis in children with acquired immune deficiency syndrome. Histopathologic and immunocytologic features. AB - Hepatic morphology and immunocytology were evaluated in 4 children with clinical and immunologic characteristics of the acquired immune deficiency syndrome or acquired immune deficiency syndrome related complex. All 4 children had hepatomegaly and increased serum alanine and aspartate aminotransferase activity. Both lobular and portal changes were noted. Lymphocytic infiltration, piecemeal necrosis, hepatocellular and bile duct damage, sinusoidal cell hyperplasia, and endothelialitis were prominent. Vesicular rosettes in sinusoidal lymphocytes and tubuloreticular structures in sinusoidal endothelial cells were demonstrated by electron microscopy. The lymphocytic infiltrate in both the lobular and portal spaces was characterized by a relative increase of cytotoxic/suppressor (T8) cells. Hepatitis may be a common feature of pediatric acquired immune deficiency syndrome and acquired immune deficiency syndrome-related complex. Although the histopathologic changes are consistent with chronic active hepatitis, the specific pathogenesis remains to be determined. MH - Acquired Immunodeficiency Syndrome/COMPLICATIONS/IMMUNOLOGY/*PATHOLOGY ; Biopsy ; Child ; Child, Preschool ; Chronic Disease ; Female ; Hepatitis/ ETIOLOGY/IMMUNOLOGY/*PATHOLOGY ; Hepatomegaly/ETIOLOGY ; Human ; Infant ; Liver/IMMUNOLOGY/*PATHOLOGY ; Microscopy, Electron ; Rosette Formation ; Support, U.S. Gov't, P.H.S. ; Suppressor Cells/IMMUNOLOGY ; T Lymphocytes/ IMMUNOLOGY ; T Lymphocytes, Cytotoxic/IMMUNOLOGY SO - Gastroenterology 1986 Jan;90(1):173-81