CD4-mediated inhibiton of IL-2 production in activated T cells

The role of CD4 in T cell activation has been attributed to its capacity to increase the avidity of interaction with APC and to shuttle associated Lck to the TCR/CD3 activation complex. The results presented in this study dem onstrate that ligation of CD4 inhibits ongoing responses of preactivated T cells. Specifically, delayed addition of CD4-specific mAb is shown to inhib it Ag- or mAb-induced responses of both primary T cells and T cell clonal v ariants. The Ag responses of the latter are independent of the adhesion pro vided by CD4; thus the observed inhibition is not due to blocking CD4-MHC i nteractions. Further, analysis of the clonal variants demonstrates that CD4 -associated Lck is not essential for the inhibition observed, as anti-CD4 i nhibits responses of clonal variants, expressing a form of CD4 unable to as sociate with Lck (double cysteine-mutated CD4). The inhibition is counterac ted by the addition of exogenous IL-2, demonstrating that the block is not due to a lesion in IL-2 utilization, rather its production. It is demonstra ted that the delayed addition of anti-CD4 results in a rapid reduction in s teady-state levels of IL-2 mRNA in both primary T cells and clonal variants .