B7-1 SYNERGIZES WITH INTERLEUKIN-12 IN INTERLEUKIN-2 RECEPTOR-ALPHA EXPRESSION BY MOUSE T-HELPER-1 CLONES

Expression of interleukin-2 receptor alpha (IL-2R alpha) is critical t o induce interleukin (IL)-2-dependent proliferation of T helper (Th)1 clones. The IL-2R alpha expression of Th1 clones is known to be up-reg ulated by IL-12. Go-stimulation via CD28/CTLA-4 is also known to be im portant for efficient activation of CD4(+) T cells. In the present exp eriments, IL-12-induced enhancement of IL-2R alpha expression of Th1 c lones stimulated with B cells as antigen-presenting cells (APC) is sup pressed by the addition of anti-B7-1. To analyze the mechanism, Th1 cl ones were stimulated with immobilized anti-CD3 plus IL-12 in the prese nce or absence of chinese hamster ovary cells that express mouse B7-1 (B7-1CHO) and the enhancement of IL-2R alpha expression induced by the cc-stimulation was analyzed. The results of these experiments indicat e that B7-1 synergizes with IL-12 in IL-2R alpha expression of the Th1 clone stimulated with anti-CD3, although B7-1CHO alone did not enhanc e IL-2R alpha expression of the clones. B7-1 stimulation is not mediat ed by the enhancement of IL-2 production: B7-1 enhancement of IL-2R al pha expression was FK506 resistant, while the inclusion of FK506 abrog ated IL-2 production of the Th1 cells. B7-1 co-stimulation did not sta bilize IL-2R alpha mRNA, but did synergize with IL-12 to enhance IL-2R alpha mRNA transcription.