MATURATION OF NEONATAL HUMAN CD4 T-CELLS .3. ROLE OF B7 CO-STIMULATION AT PRIMING

We previously reported that human naive CD4 T cells differentiate into effector cells producing type 1 (IL-2, IFN-gamma) and type 2 (IL-4, I L-5, IL-10) cytokines after priming with anti-CD3 mAb presented on irr adiated CD32-transfected mouse L fibroblasts, in the absence of exogen ous cytokine. Here we first show that the CD32 L fibroblasts act not o nly by cross-linking anti-CD3 mAb but also by providing a B7-mediated co-stimulation signal which is required for the activation of naive T cells. Using a selected anti-CD3 mAb (64.1) we next demonstrate that c olligation of CD3 and CD28 with soluble mAb is sufficient to activate highly purified naive CD4 T cells for proliferation, IL-4 mRNA express ion, IL-4 secretion, and maturation into IL-4- and IL-5-producing cell s. Finally, we show that the intensity of B7 co-stimulation at priming markedly affects the lymphokine-producing phenotype of primed cells. Indeed, cells primed on CD32-B7 double L transfectants produce much mo re IL-4 and IL-5 and slightly less IFN-gamma than those primed on CD32 L cells. The enhanced IL-4/IL-5-producing capacity of cells primed on CD32-B7 L fibroblasts may be related to increased IL-4 production dur ing priming. It is suggested that the maturation of naive T cells alon g the T(h)2 or T(h)1 pathway may be regulated by the level of B7 expre ssed on APC.