Mechanism of the age-related decline in lymphocyte proliferation: role of IL-2 production and protein synthesis.
Although an age-related decline in mitogen-induced proliferation in spleen lymphocytes has been reported by numerous investigators, the molecular mechanism responsible is unknown. In this study, we compared the mitogen-induced proliferation, IL-2 production, and protein synthesis in spleen lymphocytes isolated from 4, 12, 20, and 30 month-old male Fischer F344 rats. IL-2 production by Con A-stimulated lymphocytes, as determined by the ability of the culture supernatants to support the growth of cultured T cells, declined over 72% between 4 and 30 months of age. This decline in IL-2 production paralleled a similar decrease in proliferation. Early protein synthesis by Con A-stimulated spleen lymphocytes was determined by measuring the incorporation of [3H]-valine into acid insoluble material, and this dropped 74% between 4 and 30 months of age. There was a strong correlation between the age-related decline in the three parameters tested. Based on these results, we propose that the age-related decline in protein synthesis may be the molecular basis for the similar decrease in IL-2 production and mitogenesis.
D000375:Aging; D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D014176:Protein Biosynthesis; D051381:Rats; D011916:Rats, Inbred F344
D007376:Interleukin-2; D003208:Concanavalin A