Preincubation with anti‐CD4 influences activation of human T cells by subsequent co‐cross‐linking of CD4 with CD3

Under physiological conditions, T cell activation by major histocompatibility complex (MHC)‐anti‐ gen complexes requires engagement of both the T cell receptor (TcR) and the CD4 (or GD8) accessory molecules. It has been shown, however, that ligation of CD4 and GD8 can also inhibit T cell activation in an MHG‐independent way. Therefore, the role of CD4 in T cell activation and the mechanism of the suppression of T cell functions by anti‐CD4 are as yet unclear. We activated T cells by CD4/CD3 co‐cross‐linking and studied the effect of preincubation with anti‐CD4 on this activation. We show here that anti‐GD4 affects T cell activation in a complex, time‐dependent manner. Whereas short preincubations with anti‐GD4 usually enhanced T cell proliferation in response to subsequent co‐cross‐linking of CDS with GD4, longer preincubations led to its decrease. The observed suppression of proliferation after a long preincubation with anti‐CD4 was apparently due to impairment of TcR signaling, as assessed by measurement of Ca 2+ mobilization and tyrosine phosphorylation in T cells. These results add a temporal element to the previously observed synergism between the TcR and CD4 in T cell activation.