title: Restricted expression of mitogen-induced high affinity IL-2 receptors in aging mice.
abstract: Several lines of indirect evidence suggest that the number and/or affinity of IL-2R expressed by activated T lymphocytes declines with age and that this decline is implicated in the age-related proliferative impairment of Ag or mitogen-stimulated T cells. In an attempt to provide a direct demonstration of such a defect, various experimental approaches were used to analyze the expression of high and low affinity IL-2R as well as their functional properties in relation to age in purified populations of murine T lymphocytes. IL-2R were induced by Con A-activation which involves a transmembrane signaling mechanism or by exposure to phorbol dibutyrate (PDBu) which bypasses such a pathway. Consistent with the previously reported age-related defect in signal transduction, a major deficiency in the expression of high affinity IL-2R was observed in mitogen-activated cells derived from aged animals. As expected, PDBu-induction circumvented the transmembrane signaling defect and resulted in the restoration of a measurable amount of high affinity IL-2R expressed by cells from aged mice early after activation. The functional properties of the IL-2R expressed as a consequence of Con A or PDBu induction were investigated by assessing the proliferative response induced through the high affinity IL-2R as compared to that mediated by the beta-chain alone. Although Con A-induction resulted in a decreased expression of high affinity IL-2R by T lymphocytes derived from aged mice, the ability of these receptors as well as that of their beta-chain component to transmit a proliferative signal was identical in both age groups. In contrast, PDBu induced in both cell populations the expression of functionally aberrant IL-2R, unable to signal for proliferation unless excessively high concentrations of rIL-2 were available. The quantitative minimal estimate of the frequency of Con A-activated, IL-2-responsive cells showed a fourfold age-associated decrease, confirming the inability of a subpopulation of T lymphocytes from aged mice to express a sufficient density of high affinity IL-2R as a consequence of mitogenic activation.
authors.affiliation: Clinical Immunology Section, National Institute on Aging, Baltimore, MD 21224.
authors.forename: J J
authors.initials: JJ
authors.lastname: Proust
authors.forename: D S
authors.initials: DS
authors.lastname: Kittur
authors.forename: M A
authors.initials: MA
authors.lastname: Buchholz
authors.forename: A A
authors.initials: AA
authors.lastname: Nordin
mesh_terms: D000375:Aging; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003208:Concanavalin A; D007376:Interleukin-2 / Q000378:metabolism / Q000502:physiology; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008934:Mitogens; D015240:Phorbol 12,13-Dibutyrate; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000187:drug effects; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology
chemical_list: D007376:Interleukin-2; D008934:Mitogens; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D003208:Concanavalin A; D015240:Phorbol 12,13-Dibutyrate