Anti-CD4 monoclonal antibodies enhance phorbol 12-myristate, 13-acetate-induced activation of human T cells

Evidence exists which indicates that the T cell differentiation molecule CD4 may interact with nonpolymorphic determinants of major histocompatibility complex (MHC) class II antigens on accessory cells to stabilize the formation of a ternary complex formed by the T cell receptor (CD3-TcR), antigen, and MHC class II restriction element. However, there is also evidence which suggests alternative or additional functional roles of CD4 in the delivery of signals to T cells independent of MHC class II recognition. In the present study, we examined different anti-CD4 monoclonal antibodies (mAbs) for their ability to influence lymphocyte proliferation induced by phorbol 12-myristate, 13-acetate (PMA). We found that the response of human peripheral blood mononuclear cells to PMA could be enhanced by some anti-CD4 mAbs (OKT4, OKT4A) but not by others (G17-2). This enhancement was due neither to a direct action of the mAbs on the monocytes nor to intercellular crosslinking through an Fc-Fc receptor interaction. We also found that the binding of anti-CD did not influence the down-regulation of CD4 expression induced by PMA, ruling out any correlation between increased stimulation and CD4 modulation. Our results, taken together with those recently published on the ability of a soluble anti-CD4 mAb (B66) to induce lymphocyte activation by itself, provide evidence that CD4 antigen plays a positive functional role in T cell stimulation in addition to stabilizing the antigen-antigen receptor interaction.