IL-6 INDUCES TARGET-CELL RESISTANCE TO HIV-SPECIFIC CYTOTOXIC LYSIS

Interleukin-6 (IL-6) is a pleiotropic cytokine with multiple immunomod ulatory functions. Although IL-6 enhances cytotoxic effector cell func tion in vitro, we report the paradoxical effect of IL-6-induced resist ance of target cells to lysis by cytotoxic T lymphocytes (CTL). The CT L system employed autologous, Epstein-Barr virus-transformed B lymphob lastoid target cells infected with vaccinia virus vectors carrying the envelope gene from the human immunodeficiency virus (HIV). Effector c ells were fresh peripheral blood mononuclear cells from HIV+ individua ls. Resistance was induced by exposing B cell line targets to exogenou s 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 revers ible 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 produc ed by the cell lines. These findings have significance for the utility and interpretation of CTL assays as in vitro correlates of T cell com petence and may be significant in vivo in situations such as HIV infec tion where IL-6 production is increased.