Unexpected high incidence of tumours in thymectomized mice treated with anti-lymphocytic globulin and Mycobacterium leprae.
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Biomedical subjects
Publications and source records attributed to M S Hirsch.
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Rabbit anti-mouse thymocyte serum suppressed host cell-mediated responsiveness to intravenously administered vaccinia virus, thereby augmenting the morbidity and mortality of this infection. It did not affect either humoral antibody or interferon production in response to vaccinia virus. No effects were noted on primary or secondary immunity to intracerebral virus inoculation.
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Antithymocyte serum, when administered neonatally to mice, delayed the maturation of the lymphoid system, permitting development of cellular tolerance to LCM virus at an older age than is ordinarily possible. Humoral antibody formation was not prevented and the animals exhibited the paradox of high titers of both circulating virus and antibody. This, in turn, was followed by a chronic immunopathologic glomerulonephritis in most animals. Some animals developed wasting disease between 1 and 2 months of age, characterized by reticular cell hyperplasia and widespread infiltration into tissues and organs.
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Virus-specific cytotoxic T lymphocytes (CTL) which kill virus-infected cells are thought to be a major host defence against viral infections. Here we report the existence of human immunodeficiency virus (HIV)-specific CTL in persons infected with this virus, the aetiological agent of AIDS (acquired immunodeficiency syndrome). Recombinant HIV-vaccinia viruses were used to express HIV antigens in B-cell lines established from subjects seropositive for HIV and seronegative controls. Circulating lymphocytes capable of killing HIV env-expressing autologous B cells were detected in eight of eight seropositive subjects; in addition, at least three seropositive subjects demonstrated gag-specific cytotoxic responses. No HIV-specific cytotoxicity was observed in seronegative subjects. Selective inhibition of the env-specific cytotoxicity by a CD3-specific monoclonal antibody indicates that the effectors are T cells. This demonstration of a cytotoxic T-cell immune response to HIV in infected individuals should prove useful in investigating the immunopathogenesis of HIV infection further and in evaluating AIDS vaccine strategies.
Seropositivity to human T-cell lymphotrophic virus-III (HTLV-III) can have profound implications for the individual in whom it is detected. Simple and reliable tests are needed to confirm positivity by screening assays. In this study, detection of human antibodies by indirect immunofluorescence (IFA) on acetone-fixed HTLV-III infected H9 cells was evaluated in blood donors, patients with infectious or auto-immune diseases, and men with or at high risk for developing acquired immune deficiency syndrome (AIDS). Specific and nonspecific patterns of immunofluorescent reactivity were distinguished easily. None of 98 serums from blood donors was positive, while two of 33 serums from patients attending an infectious disease clinic, both homosexual men, were positive. Ninety-six percent of 24 serums from men with AIDS, 87 percent of 70 serums from men with lymphadenopathy, and 50 percent of 135 serums from healthy gay men were positive. These results paralleled those obtained by Western blotting and membrane immunofluorescence. In contrast, 11 and 4 percent, respectively, of these serums were judged as borderline or not interpretable by an enzyme-linked immunosorbent assay (ELISA). Of these serums, those that were positive by IFA were positive by Western blots, and 16 of the 17 IFA-negative serums were negative by Western blots. These studies indicate that IFA is a sensitive and specific assay for HTLV-III antibodies in human serums.
Viral interactions may occur whenever a host is infected simultaneously with two viruses. Persons at high risk for acquired immunodeficiency syndrome (AIDS) may provide a substrate for such interactions. These could include complementary immunosuppression, potentiation of infection by altered receptors or genetic complementation, phenotypic mixing, or genetic recombination. The possibility of such interactions should be considered in the pathogenesis of AIDS.
The current epidemic of acquired immunodeficiency syndrome (AIDS) poses a major threat to our population. Urgently needed are both a vaccine to prevent infection with the etiologic retrovirus, human immunodeficiency virus (HIV), and safe, effective antiviral agents to treat those individuals already infected. The elucidation of viral replicative mechanisms has allowed the development and testing of several agents active against HIV in vitro. Inhibitors of reverse transcriptase that have demonstrated activity include azidothymidine, phosphonoformate, antimoniotungstate (HPA-23), and suramin. Ribavirin and recombinant interferon alpha-A (IFN-alpha-A) also inhibit HIV replication, although their mechanisms of action are less clear. All of these compounds are undergoing early clinical trials in patients with HIV infection. The identification of immunogenic viral proteins may allow the development of one or more subunit vaccines against HIV. Studies are underway to clone appropriate viral genes and incorporate the expressed proteins into vectors for administration. Laboratory models, e.g., chimpanzees, will be inoculated with candidate vaccines and, if successful, this will be followed by clinical trials for safety and efficacy in appropriate human populations seronegative for HIV. Although important problems, such as virus envelope protein variability, need to be addressed, efforts to develop effective vaccines may well prove successful in the years ahead.
Several aspects of C-type oncornavirus-lymphocyte interactions in the mouse are reviewed: 1) immunological abnormalities induced by C-type viruses, particularly immunosuppression and autoimmunity; 2) activation or amplification of endogenous C-type viruses during immunological reactions; and 3) the immune responses to these endogenous oncornaviruses. A unifying hypothesis is proposed to relate various interactions between lymphocytes and C-type oncornaviruses.
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