Molecular analysis of the dissociation between IL-2 production and proliferation in a response of a T cell clone to the antigen presented by B cells.
Using B cells as APC, antigen specific responses of two murine T cell clones, 34-7F and 35-8H, were analyzed. 34-7F cells produced IL-2 but failed to proliferate, whereas 35-8H cells both produced IL-2 and proliferate. The antigenic stimulation increased intracellular free Ca2+ concentration in both clones, but enhanced inositol phospholipid metabolism only in 35-8H cells. The treatment of 34-7F cells with PMA, an activator of protein kinase C, synergized with the antigenic stimulation to induce the proliferation of the T cells. Thus, the failure of 34-7F cells to proliferate in the Ag response appears to result from the absence of an increase in inositol phospholipid metabolism. The absence is likely due to the defect in B cells as APC, inasmuch as the antigenic stimulation of 34-7F cells with whole spleen cells induced increases in inositol phospholipid metabolism and proliferation. The PMA treatment synergized with the Ag on B cells to enhance IL-2R expression, which was not inhibited by the addition of nifedipine, a calcium channel blocker. The agent inhibited the IL-2 production. Taken together, the results in the present experiments suggest the association of IL-2 production with increases in intracellular free Ca2+ concentration but not in inositol phospholipid metabolism, and that of IL-2R expression with increases in the metabolism but not in intracellular free Ca2+ concentration.
Kakiuchi
T
T
Department of Allergology, University of Tokyo, Japan.
Mizuguchi
J
J
Nariuchi
H
H
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009543:Nifedipine / Q000494:pharmacology; D010047:Ovalbumin / Q000276:immunology; D010716:Phosphatidylinositols / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate
D007376:Interleukin-2; D010716:Phosphatidylinositols; D015375:Receptors, Interleukin-2; D010047:Ovalbumin; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium