Preferential enhancement by 2-mercaptoethanol of IL-2 responsiveness of T blast cells from old over young mice is associated with potentiated protein kinase C translocation.
Certain thiol compounds have been shown to enhance the T cell-dependent immune response of mice in vivo and the proliferation of T cells in vitro. The magnitude of augmentation is often greater in old than young mice. We hypothesized that the metabolic process that is preferentially up-regulated by thiol compounds in T cells from old mice may reflect a rate-limiting process which contributes to immunosenescence in aging mice. Because IL-2 dependent T cell proliferation in vitro is positively correlated with the strength of T cell-dependent immune response in vivo, we investigated the effects of 2-ME on (a) IL-2 synthesis in vitro, (b) the IL-2-IL-2R binding interaction, and (c) the translocation of PKC from the cytosol to the membrane in Con A-activated splenic T cells from young and old C57BL/6 and C57BL/s mice. The results demonstrated that 2ME does not preferentially enhance the synthesis or secretion of IL-2. Neither the binding affinity of IL-2 to the IL-2R nor the number of receptors on activated T cell blasts differed between young and old mice. At the post-receptor binding level, the magnitude of the translocation of PKC from the cytosol to the membrane was significantly greater in the T blast cells from old than young mice. The preferential enhancement of IL-2-dependent proliferation of T cells from old mice by 2ME is therefore associated with a potentiated translocation of PKC. This would suggest that the metabolic event involved in the translocation of PKC in T cells is vulnerable to aging.
Fong
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TC
Department of Microbiology and Immunology, UCLA School of Medicine 90024.
Makinodan
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D000375:Aging / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008623:Mercaptoethanol / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011493:Protein Kinase C / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D008623:Mercaptoethanol; D011493:Protein Kinase C