title: Signaling via CD28 costimulates lymphokine production, but does not reverse unresponsiveness to interleukin-2 in anti-CD3 triggered Th1 cells.
abstract: Previously, it has been described that the ability of murine Th1 cells to proliferate in response to exogenous interleukin (IL)-2 is blocked when these cells are exposed to immobilized anti-CD3 antibodies. In the present study we examined whether simultaneous triggering of the T cell antigen CD28 can prevent the induction of unresponsiveness to IL-2 in Th1 cells. We report that costimulation of Th1 cells with anti-CD28 monoclonal antibodies (mAb) did not overcome unresponsiveness to IL-2 induced by various amounts of immobilized anti-CD3 antibodies. However, stimulation with anti-CD28 mAb strongly augmented IL-2 and interferon-gamma production in anti-CD3-exposed Th1 cells. Thus, despite the fact that anti-CD28 mAb is a potent costimulus for lymphokine production, signaling through CD28 does not seem to be sufficient to trigger proliferation in Th1 cells activated via the T cell receptor. These data suggest the existence of at least three signals to trigger Th1 cell activation. The first is mediated by ligation of the T cell receptor. One cosignal, delivered by the CD28 molecule, leads to IL-2 production. A third, still undefined, signal is required for proliferation in response to IL-2.
authors.affiliation: Institut für Klinische Mikrobiologie, Universität Erlangen-Nürnberg, FRG.
authors.forename: F
authors.initials: F
authors.lastname: Sommer
authors.forename: M
authors.initials: M
authors.lastname: Röllinghoff
authors.forename: M
authors.initials: M
authors.lastname: Lohoff
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001667:Binding, Competitive; D018106:CD28 Antigens; D017252:CD3 Complex; D002460:Cell Line; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D015398:Signal Transduction / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D007371:Interferon-gamma