Interleukin 12 (IL-12), also known as natural killer cell stimulatory factor (NKSF) or cytotoxic lymphocyte maturation factor (CLMF), is a pleiotropic cytokine originally identified in the medium of a human B-lymphoblastoid cell line (1-3).
Biologically active mouse IL-12 is a disulfide-linked, 70 kDa (p70) heterodimeric glycoprotein composed of a 40 kDa (p40) subunit and a 35 kDa (p35) subunit. While the p40 and p35 subunits by themselves do not have IL-12 activity, the p40 homodimer has been shown to bind the IL-12 receptor and is an IL-12 antagonist (4, 5). Mature mouse p35 subunit is composed of 193 amino acid (aa) residues and contains seven cysteines plus one potential N-linked glycosylation site (6). Mature mouse p40 subunit has 313 aa, with 13 cysteines and five potential N-linked glycosylation sites (6). Mouse p35 and p40 subunits show 63% and 72% aa identity, respectively, to the human p35 and p40 subunits (3, 6). Although mouse IL-12 is active on both human and mouse cells, human IL-12 is only active on human cells.
IL-12 has been shown to have multiple effects on T lymphocytes and natural killer (NK) cells. Some of these effects include the induction of IFN-γ and TNF production by T and NK cells, the enhancement of cytotoxic activity of T and NK cells and the stimulation of T and NK cell proliferation. IL-12 has also been shown to be a central mediator of the cell-mediated immune response by promoting Th1 development (7-11).
Cell surface staining for IL-12 on a human monocytic and a mouse macrophage cell line has been reported, suggesting that membrane-associated IL-12 may exist (12). Cells known to produce IL-12 include macrophages, dendritic cells, monocytes, Langerhans cells, neutrophils, and keratinocytes. Although a human B cell line has been shown to produce IL-12(2), fresh B cells are apparently not producers of IL-12.
Kobayashi, M. et al. (1989) J. Exp. Med. 170:827.
Stern, A.S. et al. (1990) Proc. Natl. Acad. Sci. USA 87:6808.
Gubler, U. et al. (1991) Proc. Natl. Acad. Sci. USA 88:4143.
Gillessen, S. et al. (1995) Eur. J. Immunol. 25:200.
Ling, P. et al. (1995) J. Immunol. 154:116
Schoenhaut, D.S. et al. (1992) J. Immunol. 148:3433.
Trinchieri, G. (1995) Annu. Rev. Immunol. 13:251.
Pudda, P. et al. (1997) J. Immunol. 159:3490.
Windhagen, A. et al. (1996) J. Immunol. 157:1127.
Mehrotra, P.T. et al. (1998) J. Immunol. 160:2637.
Wolf, S. F. et al. (1994) Stem Cells 12:154.
Fan, X. et al. (1996) Biochem. Biophys. Res. Commun. 225:1063.