ACTIVATION OF CD4(-LYMPHOCYTES FROM INTERLEUKIN 2-DEFICIENT MICE BY COSTIMULATORY B7 MOLECULES() T)

Interleukin 2 (IL-2)-deficient (IL-2(-/-)) mice develop hemolytic anem ia and chronic inflammatory bowel disease. Importantly, the induction of disease in IL-2-deficient mice is critically dependent on CD4(+) T cells. We have studied the requirements of T cells from IL-2 deficient mice for costimulation with B7 antigens, Stable B7-1 or B7-2 chinese hamster ovary (CHO) cell transfectants could synergize with anti-CD3 m onoclonal antibody (mAb) to induce the proliferation of CD4(+) T cells from IL-2(-/-) mutant mice. Further mechanistic studies established t hat B7-induced activation resulted in surface expression of the gamma chain of the IL-2 receptor, B7-induced proliferation occurred independ ently of IL-4 and was largely independent of the common gamma chain of the IL-2, IL-4, IL-7, IL-9, and IL-15 receptors. Finally, anti-B7-2 b ut not anti-B7-1 mAb was able to inhibit the activation of IL-2(-/-) T cells induced by anti-CD3 mAb in the presence of syngeneic antigen-pr esenting cells, The results of our experiments Indicate that IL-2(-/-) CD4(+) T cells remain responsive to B7 stimulation and raise the poss ibility that B7 antagonists have a role in the prevention/treatment of inflammatory bowel disease.