Nobukazu Kashima

Molecular Analysis of the Interleukin‐2 System

Interleukiti-2 (IL-2)., also referred to as T-cell growth factor, is a major lymphokine for T lymphocytes and delivers various signals by interacting with specific cell surface receptors (IL-2R) (Morgan et al. 1976, Stnith 1984). Since the discovery of this immunoregulatory molecuoe (Morgan et al. 1976). numerous biological activities have been ascribed to IL-2, including stimulation of T-cell clones for long-term in vitro growth (Morgan et al. 1976, Gillis & Smith 1977), induction of cytotoxic T-cell reactivity (Gillis et al. 1979). augmentation of natural killer cell activity (Henney et al. 1981), generation of lymphokine-activated killer (LAK) cells (Gritnm et al. 1982) and B-cell growth and differentiation (Kishi et al. 1985, Mond et al. 1985). Furthermore, recent reports indicate that human IL-2 delivers reversed growth signal in neoplastic T cells (Hatakeyama et al. 1985, Sugamura et al. 1985). In T cells, both IL-2 and IL-2R gene expressions require triggering of T3/Ti complex by antigen. Thus, clonal growth and expansion of antigen-specific T cells appear to occur via a process of signal transduction wherein the specific antigen/MHC-T3/Ti interaction is converted into a pathway of cellular growth mediated by the IL-2 system (Figure 1). Expression of IL-2 in vivo therefore seems to be one of the most crucial events in the developmental control and amplificatioti ofthe T cell-mediated immune system (see reviews by Smith 1980, 1984). The molecular and genetic events leading to the onset of cellular growth and/or differentiation of T cells remain totally obscure at the present time. More recently, much attention has been focused on the clinical potential of IL-2 in cancer Immunotheraphy (Rosenberg et a!. 1985). It might be pointed out