We have investigated the immunopathogenic mechanisms responsible for CD4+ T cell depletion. Apoptosis has never been observed in mononuclear cells freshly isolated from peripheral blood. Evidence for apoptosis has been observed in lymph node sections from HIV infection individuals. Macrophages containing apoptotic bodies have been observed in lymphoid tissue sections. Bone marrow derived dendritic cells (DC) are comprised of 2 populations only one of which is infectable by HIV. This latter population may in fact be a monocyte lineage cell. DC can bind HIV and pass infection on to unstimulated CD4+ T cells. We have demonstrated that the HLA complex influences the expressed T-cell receptor repertoire. Significant differences in the expression of the Vbeta repertoire have been observed in CD4+ and CD8+ T cell subsets. We have demonstrated that distinct sets of Vbeta families are perturbed in circulating CD4+ T cells in HIV infected individuals. These results may be consistent with the presence of a superantigen. LFA-1/ICAM-1-2-3 pathway of cell-to-cell adhesion regulates HIV-mediated syncytia formation. ICAM-1, ICAM-2 and ICAM03 molecules function as counter-receptors for LFA-1 in the process of HIV-mediated syncytia formation. Cyclosporine A (CsA) exerts a significant inhibition (60-80%) on HIV infection in vitro at concentrations corresponding to easily tolerated serum levels of CsA in the treatment of other diseases. Suboptimal concentrations of CsA and AZT cooperate in suppressing HIV-1 infection in vitro.
