Receptors for T-Cell Growth Factor: Structure, Function and Expression on Normal and Neoplastic Cells

Abstract

“During the years since its discovery (Morgan et al., 1976), the preception of T-cell growth factor (TCGF), also called Interleukin-2 (IL-2),” an in vitro novelty has given way to an appreciation of its crucial role both in the immune response and in the etiology and potential therapy of a number of diseases. In addition to playing a pivotal role in the culturing and cloning of T cells (Gillis and Smith, 1977; Schreier et al., 1980), TCGF potentiates the release of a number of other important lymphokines, including γ-interferon (γ-IFN) (Farrar et al., 1981; Kasahara et al., 1983), B-cell growth factor (BCGF) (Howard et al., 1983), and B-cell differentiation factor (BCDF) (Inaba et al., 1983). Moreover, TCGF or defects in its production or function have been implicated in such pathological states as congenital and acquired immunodeficiency (Palladino et al, 1984; Flomenberg et al, 1983; Harel-Bellan et al., 1983; Stötter et al, 1980; Thoman and Weigle, 1982), autoimmunity (Altman et al, 1981; Dauphinée et al., 1981; Linker-Israeli et al., 1983), and cancer (Gootenberg et al., 1981; Rey et al, 1983). Indeed, the receptor for this growth factor is expressed on the cells of several types of neoplasms (see Section VII), raising the question of whether its presence in such instances is fortuitous or physiologically significant. From the viewpoint of clinical therapy, several reports have appeared demonstrating the efficacy of TCGF in promoting in vitro and in vivo activity of alloreactive (Kern et al,1981) and tumor-reactive T-cells as well as natural and lymphokine-activated killer populations (Lotze et al, 1980, 1981; Wagner et al., 1980; Gillis and Watson, 1981; Cheever et al., 1982; Hefeneider et al., 1983; Eberlein et al., 1982; Rosenberg et al., 1983; Paetkau et al., 1982; Merluzzi et al., 1983; Henney et al., 1981, Donohue et al., 1984; Grimm et al., 1983).