INVOLVEMENT OF THE CD4 MOLECULE IN A POST-ACTIVATION EVENT ON T-CELL PROLIFERATION

A monoclonal antibody (mAb) directed to a human leukocyte 55-kDa cell surface molecule with identical cellular distribution and biochemical properties to the CD4 was able to inhibit T cell proliferation induced either in a mixed lymphocyte culture or by activation with mAb anti-CD3, anti-CD2 or phytohemagglutinin. The inhibitory effect of anti-CD4 was observed in the absence of monocytes and was directly exerted on T4+ cells. This effect on cellular proliferation appears to be due to an inhibition of a post-activation event since (a) the rise of cytoplasmic Ca2+ after activation with anti-CD3 mAb is not affected by the presence of anti-CD4 and (b) the proliferation that occurs after an activation pulse of 3 h with ionophore and phorbol myristate acetate can be inhibited when the anti-CD4 is added after the pulse period. Kinetic studies demonstrated that the inhibition of cellular proliferation by anti-CD4 mAb was observed even if the antibody was added as late as 18-24 h after initiation of the culture. The effect of this blocking anti-CD4 mAb on the interleukin (IL) 2/IL 2 receptor signalling pathways was also examined. The presence of anti-CD4 slightly affected the production of IL 2. In fact, addition of exogenous recombinant IL 2 at the initiation of the cultures did not restore the proliferative response. However, anti-CD4 had a strong inhibitory effect on the expression of IL2 receptors as analyzed by direct immunofluorescence cytometry. Taken together, these results indicate that the binding of the anti-CD4 mAb to T cells interferes with a late metabolic step being capable of abolishing the proliferative activity of fully activated cells.