Interleukin 12 And Its Receptor

Erwin Rüde, Edgar Schmitt and Tieno Germann, Institut für Immunologie, Johannes-Gutenberg Universität, Mainz, Germany

IL-12 was discovered between 1986 and 1990 independently by four groups by its costimulatory activity for T and natural killer (NK) cells. This is illustrated by the original functional designations of CLMF (cytotoxic lymphocyte maturation factor, M.

Gately et al) and NKSF (natural killer cell stimulatory factor, G. Trinchieri et al) for human interleukin 12 (IL-12) as well as TSF (T cell stimulating factor, T. Germann, E. Rüde) and IL-2RIF (IL-2 receptor inducing factor, H. Nariuchi et al) for murine IL-12.

Whereas TSF and IL-2RIF were obtained from normal splenic accessory cells or bone marrow-derived macrophages upon interaction with activated Tnl cells, NKSF and CLMF were both secreted by Epstein-Barr virus (EBV)-transformed human B cell lines activated by phorbol ester. The human factors could be produced and purified in amounts sufficient for N-terminal sequence analysis. It became apparent that NKSF and CLMF comprised two polypeptide chains, IL-12p40 and IL-12p35. Cloning of both proved the identity of CLMF and NKSF. The designation IL-12 was agreed upon. The mouse IL-12 chains were then cloned by cross-hybridization to the human cDNA probes.

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