HIV TYPE 1-SPECIFIC CYTOTOXIC T-LYMPHOCYTES STIMULATE HLA CLASS-I AND INTERCELLULAR-ADHESION MOLECULE TYPE-1 EXPRESSION AND INCREASE BETA(2)-MICROGLOBULIN LEVELS IN-VITRO

Besides acting in a direct manner, cytolytic HIV-1-specific CTLs release a variety of cytokines. To assess the potential role of cytokines released by these CTLs we tested the ability of soluble products secreted by HTV-1-specific CTLs to induce HLA class I and ICAM-1 expression and to raise beta(2)-microglobulin (beta(2)M) concentrations in cell culture. To this end, supernatants were derived from HIV-1-specific CTLs incubated with autologous B lymphoblasts presenting either the cognate HIV-1 epitope or a control peptide. Cell lines and peripheral blood mononuclear cells (PBMCs) were incubated with these supernatants for 24-48 hr. Similarly, cells were cocultured with CTLs and their targets. This study demonstrates that in parallel with lysis of their cognate target, HIV-1-specific CTLs secreted products that stimulated HLA class I and ICAM-1 expression on cell lines and PBMCs. As few as 1000 CTLs significantly induced the expression of these molecules. In addition, secreted products of HIV-specific CTLs enhanced beta(2)M release by PBMCs and Jurkat cells. These effects were mediated primarily by IFN-gamma and suggest that HIV-specific CTLs may contribute to increased HLA class I expression in infected tissue and elevated ICAM-1 and beta(2)M concentrations in serum and cerebrospinal fluid of infected individuals.