Blockade of the interleukin-2 receptor by anti-Tac antibody: inhibition of human lymphocyte activation.
We have previously shown that monoclonal anti-Tac antibody inhibits the proliferation of interleukin-2 (IL-2) dependent human continuous T cell lines. Further, we have shown that anti-Tac specifically blocks greater than 95% of the binding of radiolabeled II-2 to a continuous T cell line. In view of these data, we suggested that anti-Tac antibody may bind to and block the human T cell receptor for IL-2. We now report the effects of anti-Tac on the activation of human peripheral blood T lymphocytes. We find that anti-Tac: 1) blocks T cell proliferation induced by soluble antigens (80-90%), autologous antigens (90%) and alloantigens (75-90%); 2) partially inhibits T cell proliferation induced by mitogenic lectins, including Concanavalin A (50-88%), pokeweed mitogen (40-87%), and phytohemagglutinin (20-80%); 3) abrogates (greater than 95%) the generation of cytolytic T lymphocytes in allogeneic cell cocultures, but does not inhibit killing by cytolytic T lymphocytes once formed; 4) and inhibits T cell dependent pokeweed mitogen activated B cell immunoglobulin production (78-95%). We further demonstrate that anti-Tac inhibition of proliferation is not secondary to diminished production of IL-2. Finally, in antigen induced T cell proliferative assays, we demonstrate that the addition of highly purified IL-2 reverses the inhibitory effects of anti-Tac. These data are consistent with the hypothesis that anti-Tac recognizes the human IL-2 receptor and illustrate ways in which this antibody can be used to modulate the human immune response.
D000911:Antibodies, Monoclonal / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002455:Cell Division; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D010835:Phytohemagglutinins / Q000494:pharmacology; D011043:Pokeweed Mitogens / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000276:immunology*; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D007519:Isoantigens; D010835:Phytohemagglutinins; D011043:Pokeweed Mitogens; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D003208:Concanavalin A