Research is divided into studies concerning the regulation of i) humoral an cellular immune responses to HIV-1 envelope glycoproteins, ii) virus replication in murine models of AIDS and iii) B and T cell activation in retrovirus-induced and autoimmune diseases. i) Serum and cells were obtained from mice and humans immunized with purified recombinant envelope glycoproteins from a variety of HIV-1 isolate in order to determine the magnitude, specificity and cross-reactivity of th humoral anti-gp120 response. T cells isolated from immunized mice were studied for lymphokine production to assess activation. Results indicate that gp120-reactive B cells are primarily localized to the spleen and bone marrow of immunized mice and humans, and that the peripheral blood represents a poor source of HIV-reactive lymphocyte. ii) Two murine models of HIV infection are being examined. In the murine AIDS model, levels of T and B lymphocyte activation are being studie at the single cell level. In transgenic mice expressing gp120 proteins from HIV, the effect of immunization on tolerance induction and disease progression is being investigated. We are also studying SCID mice reconstituted with human PBL and then infected with HIV to analyze the degree of protection conferred by various immunization regimens. iii) We have been studying the number and antigenic specificity of B an T lymphocytes activated in patients and mice with SLE and AIDS. Results indicate that two processes - polyclonal activation and (auto) antigen specific immune stimulation - combine to induce the humoral abnormalities found in disease states. Murine models of these diseases are being used to analyze the specificity and cross-reactivity of activated B cells. This work is also providing considerable insight into the degree to which HIV-1 specific B cells are activated in patients with ARC and AIDS.
