IL-6 induces target cell resistance to HIV-specific cytotoxic lysis.
Interleukin-6 (IL-6) is a pleiotropic cytokine with multiple immunomodulatory functions. Although IL-6 enhances cytotoxic effector cell function in vitro, we report the paradoxical effect of IL-6-induced resistance of target cells to lysis by cytotoxic T lymphocytes (CTL). The CTL system employed autologous, Epstein-Barr virus-transformed B lymphoblastoid target cells infected with vaccinia virus vectors carrying the envelope gene from the human immunodeficiency virus (HIV). Effector cells were fresh peripheral blood mononuclear cells from HIV+ individuals. Resistance was induced by exposing B cell line targets to exogenous IL-6, or via an autocrine pathway in which IL-6 was secreted by the target cells themselves. The IL-6 effect was dose dependent and reversible by antibody to IL-6. A large proportion of B cell lines from HIV+ individuals produced IL-6, and the lysis of HIV envelope-expressing B cell targets was inversely proportional to the amounts of IL-6 produced by the cell lines. These findings have significance for the utility and interpretation of CTL assays as in vitro correlates of T cell competence and may be significant in vivo in situations such as HIV infection where IL-6 production is increased.
Liu
M
M
Department of Microbiology and Immunology, UCLA School of Medicine 90095-1752, USA.
Martinez-Maza
O
O
Johnson
M T
MT
Fan
J
J
Kishimoto
T
T
Plaeger
S
S
D000328:Adult; D002472:Cell Transformation, Viral; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D004854:Herpesvirus 4, Human; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D014616:Vaccinia virus
D015850:Interleukin-6