Autoantibodies to lymphocytes and their relationship to the number of CD4 T lymphocytes in HIV infection

The knowledge about on pathogenesis of HIV infection suggests that the cytopathic effect of the virus on CD4 T lymphocytes is not the only cause of their death. A lot of data indicate that autoantibodies and cytotoxic lymphocytes specific to CD4 comprise a death-causing factor for uninfected CD4 T-lymphocytes, thus playing a leading role in progression of immunodeficiency in HIV infection. The aim of this work was to study autoimmune reactions against CD4 T lymphocytes in HIV-infected patients. The study was conducted at the Udmurt Republican Center for Prevention and Control of AIDS and Infectious Diseases in Izhevsk. The levels of allogeneic and autologous anti-lymphocytic antibodies were determined in blood of 45 HIV-infected patients and 26 healthy donors, as well as CD4 T lymphocyte numbers by flow cytometry. To determine alloantibodies, we evaluated the binding of antibodies from studied plasma samples to mononuclears of healthy donors. To determine autoantibodies, their binding to autologous mononuclears was evaluated. Their detection was performed with second FITC-labeled antibodies to human IgG. The level of anti-lymphocytic antibodies was expressed as per cent of antibody-binding lymphocytes. Antibodies against allogeneic lymphocytes were found in 33% (9 out of 25) of HIV-infected persons. The number of CD4 T lymphocytes in blood of HIV-infected patients with antibodies to allogeneic lymphocytes was significantly lower than in blood samples from HIV-infected patients without these antibodies. Membrane-bound autoantibodies against lymphocytes were detected in 2 out of 20, i.e. in 10% of HIV-infected persons. Anti-lymphocytic autoantibodies, which present a cumulative pool of lymphocyte-bound autoantibodies and plasma autoantibodies, were detected in 10 out of 20 HIV-infected patients (50%). Two-factor analysis of variance revealed that both antilymphocyte antibodies and antiretroviral therapy exert an effect on the number of CD4 T lymphocytes in HIV-infected patients (two-way ANOVA, p = 0.045 and p = 0.050, respectively). Thus, autoantibodies against lymphocytes were detected in the blood plasma which significant affect the number of CD4 T-lymphocytes in blood of HIV-infected patients., A technique of plasma antibody binding to autologous lymphocytes may be applied to detect anti-lymphocytic autoantibodies, followed by their detection by flow cytometry using fluorescent labeled anti-species antibodies.