Research is divided into studies concerning the regulation of i) humoral and cellular immune responses induced by protein-based and 'naked DNA' vaccines encoding determinants expressed by the HIV-1 virus, ii) immune responses induced in virus-infected mice, or transgenic mice expressing HIV viral proteins 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 mice immunized with 'naked DNA' vaccines were studied to determine the magnitude, specificity and localization of the responses induced. T cells isolated from immunized mice were identified by their patterns of lymphokine production. Results indicate that a Th2-type cytokine response is induced by immunization with both gp120-subunit vaccines and 'naked DNA' vaccines. However, the localization of these responses is quite different. Immunization with protein antigens (in FA) led to cytokine production in the spleen and bone marrow, whereas DNA vaccination activated cells in the draining lymph nodes and peritoneum. In general, B cells were activated to secrete virus-specific antibodies at the sites of cytokine production. ii) Two murine models of HIV infection are being examined. In the murine AIDS model, levels of T and B lymphocyte activation are being studied at the single cell level. We found that MCMV infection interfered with infection by the murine AIDS virus, thereby preventing the lethal sequelae of the latter disease. In transgenic mice expressing gp120 proteins from HIV, the effect of immunization on tolerance induction and disease progression is being investigated. iii) We have been studying the number and antigenic specificity of B and T lymphocytes activated in patients and mice with SLE and AIDS. Results indicate that the pattern of cytokine activation is predictive of the nature and magnitude of the subsequent humoral response. These studies show that the relative ratio (rather than absolute number) of Th1 : Th2 type cytokine producing cells correlates with disease progression and the specific isotype of IgG antibody produced as a result of the disease processes. In HIV-infected patients, monocytes were found to be major sources of TH2-type cytokines, whereas CD4 cell count correlated witha preferential loss of such Th1 secreting cells.
