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.
Favero
J
J
Centre National de la Recherche Scientifique ER 228, Laboratoire de Biochimie des Membranes, Montpellier, France.
Dixon
J F
JF
Bishop
P C
PC
Parker
J W
JW
D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000502:physiology; D011961:Receptors, Fc / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000939:Epitopes; D011961:Receptors, Fc; D015375:Receptors, Interleukin-2; D013755:Tetradecanoylphorbol Acetate