Possible involvement of the CD4 molecule in a late activation event on CD4+ T cell proliferation in the human autologous mixed lymphocyte reaction.

CD4 monoclonal antibody (MoAb) was able to inhibit T cell proliferation induced in an autologous mixed lymphocyte reaction (AMLR). The effect of CD4 MoAb on cellular proliferation appears to be directly exerted on CD4+ T lymphocytes, and to be due to inhibition of a post-activation event, since the CD4+ T cell proliferation that occurs after an activation pulse of 24 h with autologous non-T cells could be inhibited when CD4 MoAb was added after, but not during, the pulse period, and the inhibition of autologous MLR-induced CD4+ T cell proliferation by CD4 MoAb was observed even if the Moab was added as late as 72 h after the initiation of culture. The presence of CD4 MoAb did not affect the production of interleukin 2 (IL-2). CD4 MoAb had, however, an inhibitory effect on the expression of IL-2 receptors, such that addition of exogenous IL-2 at the initiation of culture did not restore the AMLR-induced CD4+ T cell proliferation. These results indicate that the hindrance of the recognition of HLA class II products is not the only target of the CD4 MoAb effect in the autologous MLR. Rather, the binding of CD4 MoAb to CD4+ T cells interferes with a late event because it is capable of abolishing the proliferative activity of fully activated CD4+ T cells. The data are compatible with the idea that perturbation of the CD4 molecules can transmit a negative signal to CD4+ T cells.