1392 Regulation of Tac Antigen Expression

Interleukin 2 (IL-2), 1 also known as T cell growth factor, discovered by Morgan et al. (1), is a lymphokine produced by normal peripheral blood lymphocytes after antigen or mitogen stimulation (2, 3) and is required for the proliferation and function of T cells (2, 3), natural killer cells (4-6), and cytotoxic effector cells in vitro and in vivo (7-9). In addition, IL-2 is able to induce or enhance gamma interferon production by T cells (10, 11) and granulocyte-macrophage colony-stimulating factor (Platzer, E., K. Welte, and M. A. S. Moore, manuscript in preparation). IL-2 is also produced by fresh lymphoblastic leukemic cells (12) and T cell leukemia cell lines (13). We have demonstrated that IL-2 restores partially or completely the defective proliferative response of T cells from patients with congenital immunodeficiencies (14), acquired immunodeficiency syndrome (15), and patients after bone marrow transplantation (16). Several laboratories including our own have purified IL-2 to homogeneity (17-19). Depending on the cellular source and stimulation conditions, IL-2 shows a molecular heterogeneity with molecular weights between 14,500 and 17,000 and isoelectric points between 6.8 and 8.2 (17, 20). The molecular heterogeneity is most likely due to variations of glycosylation of the molecule (18, 20). Recombinant DNA technology has provided recombinant IL-2 (21) with biochemical and biological characteristics similar to those of native IL-2 (22, 23). Recently, a murine monoclonal antibody termed anti-Tac (24) was shown to be able to block the binding of IL-2 to the IL-2 receptor-positive human T cell line H U T 102 (25), and the cellular binding site for IL-2 was demonstrated to be identical with the Tac antigen, which is a glycoprotein of 58,000 mol wt (26). OKT3 antibody recognizes 95% of peripheral blood T lymphocytes and is mitogenic in concentrations between 0.1 and 1,000 ng/ml for total T cells (27) and T cell subpopulations (28). As recently demonstrated on T cell clones (29),