Analysis of T cell activation with a non-mitogenic anti CD3 antibody and the phorbol ester TPA.
We used a non mitogenic anti CD3 antibody, termed VIT3, to study the signals required for the activation of normal resting T lymphocytes. Besides being not mitogenic, this antibody completely inhibits mitogen induced proliferative responses. In the presence of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), however, VIT3 induces DNA replication and cell proliferation comparable to PHA responses. In addition, T cells cultured with VIT3 plus TPA but not with VIT3 or TPA alone express high levels of interleukin 2 (IL-2) receptors and transferrin receptors. This co-stimulation appears to be accessory cell independent. Purified T cells respond equally well to VIT3 plus TPA as do unseparated mononuclear cells and addition of non-T cells has no enhancing effect. We conclude that the IgM antibody VIT3, although non-mitogenic by itself, still delivers a first and for the activation essential signal. In resting T cells this signal does not induce demonstrable anti-Tac antibody binding nor does it lead to a fully developed proliferative response in the presence of recombinant IL-2. Together with a second signal provided by TPA it serves, however, as a potent inducer of T cell growth.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000954:Antigens, Surface / Q000032:analysis; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008938:Mitosis; D010704:Phorbols / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000032:analysis; D011971:Receptors, Immunologic / Q000032:analysis; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007075:Immunoglobulin M; D010704:Phorbols; D010835:Phytohemagglutinins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D003208:Concanavalin A; D013755:Tetradecanoylphorbol Acetate