The role of thymus in the aging of Th cell subpopulations and age-associated alteration of cytokine production by these cells

Mouse CD4+ T cells were subdivided into two subpopulations, naive (CD44low CD45RBhigh) and memory (CD44high CD45RBlow) T cells, by flow cytometric analysis. Examination of spleen and peripheral blood of C57BL/6 mice of various ages revealed that there was a reciprocal age-associated change in these two subpopulations, i.e. naive T cells predominant in young mice decreased with age, while memory T cells increased. In order to investigate the role of the thymus in the age change of naive and memory T cells, we employed two experimental systems: radiation bone marrow chimeras constructed between young and old mice, and grafting of young or old thymus into nude mice. Data from these two experiments suggested that the young thymus has a greater ability to provide naive T cells than the old thymus, while the old thymus favors the maintenance of memory T cells rather than naive T cells. In reference to cytokine production by enriched naive and memory T cells, young naive T cells produced mainly IL-2 and young memory T cells mainly IL-4. On the other hand, in old mice, memory T cells produced twice as much IL-2 than naive T cells, although the level was significantly lower than that of young mice. In addition, old naive T cells produced twice as much IL-4 than old memory T cells. These results suggested a distinct age change in the profile of cytokine production and functional heterogeneity of two Th cell subpopulations.