title: Cytokine production by T lymphocytes from young and aged mice.
abstract: We previously have shown that T cell proliferation in response to a primary signal through the CD3 epsilon chain and a costimulatory signal via the CD28 molecule is impaired in healthy, aged mice. To determine whether age-related alterations in cytokine production might explain the reduced proliferative responses of T cells from aged mice, we examined the secretion of the major T cell immunoregulatory cytokines, IFN-gamma, IL-4, and IL-2. Splenic T cells from young (2 to 4 mo) and aged (20 to 26 mo) mice were studied. T cells were stimulated with immobilized anti-CD3 epsilon chain mAb and soluble anti-CD28 mAb for 24 h. T cells from aged mice, when compared with young controls, showed increased IFN-gamma production, no difference in IL-4 production, and decreased IL-2 production. Most IFN-gamma was produced by CD8+ T cells, whereas most IL-2 and IL-4 was produced by CD4+ T cells. Both CD4+ and CD8+ T cells from aged mice produced significantly more IFN-gamma than corresponding cells from young mice. This increased production could be accounted for by increased numbers of CD4+CD44high and CD8+CD44high T cells in aged animals. CD4+CD44high and CD8+CD44high T cells from young mice produced comparable amounts of IFN-gamma as corresponding cells from aged mice. In contrast to unseparated splenic T cells, no age-related difference in IL-2 or IL-4 production by purified CD4+ T cells was observed. Similarly, when CD4+ T cells were further separated into CD44low and CD44high subpopulations, no age-related difference in IL-2 production was found. Therefore, we found no consistent evidence that diminished production of the major T cell growth factors, IL-2 and IL-4, is responsible for the age-related decrease in the proliferation of T cell subpopulations that were stimulated in vitro through the CD3 epsilon chain and costimulated via the CD28 molecule. The physiologic relevance of increased IFN-gamma production by T cells from aged mice is unknown.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland at Baltimore 21201, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Engwerda
authors.forename: B S
authors.initials: BS
authors.lastname: Fox
authors.forename: B S
authors.initials: BS
authors.lastname: Handwerger
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D018960:Hyaluronan Receptors / Q000276:immunology; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018960:Hyaluronan Receptors; D007376:Interleukin-2; D015847:Interleukin-4