Activation of human T lymphocytes: differential effects of CD3- and CD8-mediated signals.
T cells are activated physiologically by triggering the T-cell receptor-CD3 complex. There is evidence that invariant accessory molecules on the T-cell membrane (CD8 and CD4) are involved in the major histocompatibility complex-restricted recognition process. Moreover, binding and crosslinking of these accessory molecules to the T-cell receptor-CD3 complex exerts a positive synergistic signal, as has been shown by stimulation with crosslinked antibodies. Here we demonstrate that stimulation mediated by immobilized anti-CD3/CD8 antibodies differs from stimulation mediated solely by anti-CD3. Whereas interleukin 2 receptor expression and interferon gamma production are seen to a similar extent in both cases, a second signal provided by the additional involvement of CD8 seems to be essential for interleukin 2 production and full interleukin 2 responsiveness in CD8+ T cells. This second signal is much more sensitive to inhibition by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C and cGMP/cAMP-dependent kinases. Our results also show that substantial modulation of the T-cell receptor complex and most likely CD3 phosphorylation are not essential for initiating the activation of resting T cells. Instead, we found a 22- to 24-kDa phosphoprotein whose strong phosphorylation correlated reliably with T-cell activation.
Samstag
Y
Y
Max-Planck-Institut für Immunbiologie, Freiburg, Federal Republic of Germany.
Emmrich
F
F
Staehelin
T
T
D000328:Adult; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D017252:CD3 Complex; D016827:CD8 Antigens; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D016827:CD8 Antigens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma; D011494:Protein Kinases