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 HIV-1-specific CTLs to induce HLA class I and ICAM-1 expression and to raise beta 2-microglobulin (beta 2M) 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 2M 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 2M concentrations in serum and cerebrospinal fluid of infected individuals.
Jassoy
C
C
Institute for Virology and Immunobiology, University of Würzburg, Germany.
Heinkelein
M
M
Klinker
H
H
Walker
B D
BD
D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015497:HIV-1 / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000096:biosynthesis* / Q000187:drug effects
D017077:Culture Media, Conditioned; D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma