CD4 and CD8 regulate interleukin 2 responses of T cells.

To characterize the T-cell surface molecules involved in regulation of T-cell interleukin 2 (IL-2) responses, we established several monoclonal antibodies (mAbs) that inhibit IL-2 responses of freshly isolated CD8+ T cells and the IL-2-dependent cell line CTLL-2. Here we show that two inhibitory mAbs are directed against Lyt-2 (CD8 alpha). In fact, all anti-Lyt-2 mAbs tested were able to inhibit the IL-2 response of the Lyt-2- and L3T4-deficient cell line HT-2 after transfection with a Lyt-2 cDNA clone. Similarly, anti-L3T4 mAbs inhibited the IL-2 response of CD4-transfected HT-2 cells. These inhibitory effects of anti-CD4 and anti-CD8 mAbs occur on normal T lymphocytes, since they also were observed with CD4+ and CD8+ T-cell blasts, and are specific for IL-2 responses, since IL-4 responses of CD4- and CD8-transfected HT-2 cells were not affected by the anti-CD4 and anti-CD8 mAbs. The inhibitory effects of anti-CD4 or anti-CD8 mAbs could not be explained by interference with IL-2 binding and depended on CD4 and CD8 crosslinking, because F(ab')2 or Fab plus crosslinking second antibody, but not Fab alone, were effective. A mutant Lyt-2 molecule lacking the cytoplasmic region that mediates p56lck binding could not mediate the inhibitory effect upon crosslinking. These results suggest that CD4 and CD8 mediate negative regulation of T-cell IL-2 responses via cytoplasmically associated p56lck.