SUPPRESSION OF CELL-MEDIATED AND HUMORAL IMMUNE-RESPONSES BY AN INTERLEUKIN-2-IMMUNOGLOBULIN FUSION PROTEIN IN MICE

Interleukin-2 (IL-2) plays a pivotal role in the cellular and humoral immune responses directed against foreign antigens, We characterized t he in vitro and in vivo properties of a chimeric protein consisting of mouse IL-2 fused to the mouse IgG2b Fe domains. This fusion protein b inds to IL-2 and Fc receptors and supports IL-2-dependent cell prolife ration but does not mediate lysis of IL-2 receptor-positive cells in t he presence of murine complement in vitro. However, in vivo the IL2-Ig G2b fusion protein suppresses both cellular and humoral immune respons es after immunization with sheep erythrocytes, Surprisingly, delayed h ypersensitivity is inhibited despite a dramatic increase of splenic CD 3+ and NK1.1+ lymphocytes, indicating that altered homing of IL2-IgG2b -activated lymphocytes rather than cytolysis prevents these cells from accumulating in areas of inflammation, Although in vitro the IL2-IgG2 b fusion protein does not alter proliferation of B cells in response t o mitogenic stimulation, IgM production in response to sheep erythrocy tes is profoundly inhibited in mice treated with the IL2-IgG2b fusion protein, Since no side effects are observed, the IL2-IgG2b fusion prot ein may expand the therapeutic repertoire of reagents used for the tre atment of allograft rejection and autoimmune diseases.