Cytokine production by T lymphocytes from young and aged mice

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.