Effect of T3 modulation on pokeweed mitogen-induced T cell activation: evidence for an alternative pathway of T cell activation.
Modulation of the T3 molecule on human T cells with monoclonal anti-T3 antibodies has been shown to result in the disappearance of the T3-Ti complex from the membrane and to preclude subsequent T cell activation by various mitogenic and antigenic stimuli. We have examined the effect of T3 modulation on pokeweed mitogen (PWM)-induced T cell activation. T3 modulation was accomplished by incubating peripheral blood mononuclear cells (PBMC) or mixtures of T cells and non-T cells at 37 degrees C for 18 hr in the presence of UCHT-1, a mouse IgG1 anti-T3 monoclonal antibody. Only donors whose PBMC were unresponsive to the mitogenic activity of this antibody were selected. Although T3 modulation resulted in complete to substantial inhibition of T cell proliferation induced by low PWM concentrations of 5 or 50 ng/ml, it had no effect on T cell proliferation when PWM was added at a concentration of 0.5 and 5 micrograms/ml. The results demonstrate that the higher doses of PWM can induce T cell proliferation via an alternative pathway that does not involve participation of the T3-Ti complex. In contrast, irrespective of the PWM dose added, T3 modulation almost totally inhibited PWM-induced interleukin 2 (IL 2) production. The differential effect of T3 modulation on IL 2 production and on T cell proliferation induced by high doses of PWM suggests that this alternative pathway of T cell proliferation is IL 2 independent. This suggestion was additionally substantiated by the lack of effect of anti-Tac, and anti-IL 2 receptor antibody, on PWM-induced proliferation of T3-modulated T cells. In conclusion our data demonstrate that high doses of PWM can induce T cells to proliferate via an alternative pathway that does not involve perturbation of the T3-Ti complex.
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008875:Middle Aged; D011043:Pokeweed Mitogens / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D011971:Receptors, Immunologic / Q000032:analysis; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D007376:Interleukin-2; D011043:Pokeweed Mitogens; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7