Herpesvirus saimiri induces a fatal lymphoproliferative syndrome in a variety of New World primate species. We now show that cell lines derived from PBL of the common marmoset by in vitro-immortalization with H. saimiri strain 11 represent a remarkably restricted lymphocyte population. These cell lines have NK cell function, phenotypically express both suppressor/cytotoxic (T8) and NK cell (NKH1)-associated antigens, and express a T cell receptor. This subpopulation of lymphocytes is a very minor population of cells in the peripheral blood of common marmosets (less than or equal to 3%). The specificity in the interaction between H. saimiri strain 11 and a subpopulation of common marmoset lymphocytes represents an example of a restricted viral lymphotropism and may have important implications for the disease induced by this virus in New World monkeys.
The T cell tropic retrovirus of macaque monkeys simian T lymphotropic virus type III (STLV-III) has morphologic, growth, and antigenic properties indicating that it is related to human T cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV), the etiologic agent of the acquired immune deficiency syndrome (AIDS) of humans. STLV-III has recently been shown to induce an AIDS-like disease in macaque monkeys. In this study the humoral immune responses of six experimentally infected monkeys have been characterized to determine whether certain parameters of the antibody response to the virus might be predictive of the clinical outcome of this infection. Two distinct patterns of antibody responses were found. Four animals that died within 160 d of inoculation developed low titer anti-STLV-III antibody responses that recognized only the viral envelope protein, and progressive declines in total plasma IgG levels and absolute peripheral blood T4 lymphocyte numbers. The two animals that lived longer (one died at 352 d, the other remains alive at 430 d) developed high titer anti-STLV-III antibody responses that recognized both viral envelope and core proteins, increases in total plasma IgG, and a later decrease in number of peripheral blood T4 lymphocytes. Interestingly, the single animal that has remained clinically healthy after infection was the only one to develop detectable STLV-III neutralizing antibodies.
The human immunodeficiency virus (HIV) and the closely related simian immunodeficiency virus (SIV) induce profound immune dysfunction in primate species. The present studies show that cell populations infected in vitro with SIV exhibit increases in major histocompatibility complex (MHC) class II antigen expression. Cell lines chronically infected with both the monkey and human viruses express substantially more MHC class H but not more lineage-restricted or activation antigens on their membranes than do uninfected cell lines. Furthermore, 2'-deoxy-5-iodouridine increased MHC class II antigen expression on SIV-infected cell lines in parallel with increased expression of viral antigens. MHC class II induction does not appear to be mediated through the production of a soluble factor, such as gamma interferon, by SIV-infected cells. Interestingly, studies of the kinetics of antigen expression by cell lines after SIV infection indicate that the induction of MHC class II structures is a late event. Immunoelectron microscopy revealed that MHC class II antigen is expressed not only on the surfaces of the SIV-infected cells but also on the envelope of virus particles derived from those cells. MHC antigen expression on virus-infected cells and the expression of those determinants by the virus may play a role in the pathogenesis of acquired immunodeficiency syndrome and the autoimmune abnormalities observed in HIV-infected individuals. * Corresponding author. fected with this isolate or those of H9 cells chronically infected with this isolate were used as a virus source. MAbs. Monoclonal antibodies (MAbs) reactive with Ti (24T6G12), T3 (2Ad2A2), T4 (19Thy5D7), MHC-I (W6/32), MHC-II (I-2,949), the interleukin-2 (IL-2) receptor (1HT4), and the T-cell activation antigen Ta.1 (4EL) were kindly provided by S. Schlossman (Dana-Farber Cancer Institute, Boston, Mass.). The anti-T3 MAb SP34 was provided by C. Terhorst (Dana-Farber Cancer Institute). The anti-MHC-II MAb LB3.1 was provided by J. Strominger (Dana-Farber Cancer Institute). All the anti-MHC-II MAbs used recognized HLA-DR. Cellular radioimmunoassay. Between 2 x 105 and 5 < 105
Immunologic changes associated with aging were studied by various immunologic tests in 24 aged persons (age range, 76-83) and 25 young persons (age range, 20-40). The responses to phytohemagglutinin (PHA) and concanavalin A (Con A) were depressed in the aged subjects compared to the young ones (p less than 0.05), whereas the responses to pokeweed mitogen (PWM) were similar. The activity of adhereent and non-adherent cells was assessed in various combinations. The adherent cells of aged persons were indistinguishable from those of young persons in their ability to response to Con A. Lymphocytes from the aged synthesized larger in vitro amounts of immunoglobulin than did lymphocytes from the young, when stimulated with PWM. Con A-stimulated T lymphocytes derived from aged subjects showed a variable loss of suppressor activity. The mixed lymphocyte culture reaction with mitomycin-treated allogeneic and autologous cells was also impaired in aged subjects. Such an impaired response in the aged is related to higher incidences of malignant lesions and auto-antibodies.
In the present study, T-cell subsets from aged individuals were examined by using anti-BAT (brain-associated thymocyte antigen) serum. Anti-BAT serum was raised against the human fetal brain at 28 weeks of gestation. After absorption wit AB erythrocytes, B-cell lines, and leukaemic cells, anti-BAT serum was T cell-specific but unreactive to normal B cells. The ability of anit-BAT serum-treated lymphocytes from aged individuals to respond to concanavalin A, phytohaemagglutinin, and pokeweed mitogen (PWM) was unaltered even at a high concentration. In PWM-stimulated Ig synthesis, T lymphocytes lacking the anti-BAT serum-reactive T-cell subset enhanced the PWM-stimulated Ig synthesis of autologous B lymphocytes from young individuals. The Con A-induced suppressor function of lymphocytes from aged individuals was not significantly abolished by treatment with anti-BAT serum and complement. In the autologous mixed lymphocyte reaction, the decrease in response was minimal when responder cells from aged individuals was treated with anti-BAT serum even at a high concentration. It is concluded that the T-cell subset with suppressor function is defective in aged individuals.
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