IL-2-Independent Activation of LAK Cells by a Heterodimeric Cytokine, Interleukin-12

Abstract

Interleukin-12 (IL-12) is a heterodimeric cytokine which was originally isolated from cultures of activated human B lymphoblastoid cells and called natural killer cell stimulatory factor (Kobayashi et al., 1989) or cytotoxic lymphocyte maturation factor (Stern et al., 1990). IL-12 has been shown to stimulate the proliferation of activated T cells and natural killer (NK) cells (Gately et al., 1991) and to cause interferon-γ (IFN-γ) production (Kobayashi et al., 1989; Chan et al., 1991) and enhanced NK lytic activity (Kobayashi et al., 1989; Wolf et al., 1991) by resting peripheral blood mononuclear cells (PBMC). IL-12, unlike IL-2, does not cause resting PBMC to proliferate, but it can stimulate enhanced proliferation of PBMC cultured in suboptimal concentrations of IL-2 (Gately et al., 1991). IL-12 is composed of two disulfide-bonded subunits with molecular masses of 35 and 40 kDa (Kobayashi et al., 1989; Stern et al., 1990). The cDNA encoding each of these two subunits has recently been cloned and bioactive recombinant IL-12 (rIL-12) expressed (Gubler et al., 1991; Wolf et al., 1991). Coexpression of the two subunits is required for biologically active IL-12 to be produced (Gubler et al., 1991: Wolf et al., 1991).