Activation of CD4(+) T lymphocytes from interleukin 2-deficient mice by costimulatory B7 molecules

Interleukin 2 (IL-2)-deficient (IL-2(-/-)) mice develop hemolytic anemia 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 monoclonal antibody (mAb) to induce the proliferation of CD4(+) T cells from IL-2(-/-) mutant mice. Further mechanistic studies established that B7-induced activation resulted in surface expression of the gamma chain of the IL-2 receptor, B7-induced proliferation occurred independently 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 but 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-presenting cells, The results of our experiments Indicate that IL-2(-/-) CD4(+) T cells remain responsive to B7 stimulation and raise the possibility that B7 antagonists have a role in the prevention/treatment of inflammatory bowel disease.