THE ROLE OF THYMUS IN THE AGING OF T-H CELL SUBPOPULATIONS AND AGE-ASSOCIATED ALTERATION OF CYTOKINE PRODUCTION BY THESE CELLS

Mouse CD4(+) T cells were subdivided into two subpopulations, naive (C D44(low) CD45RB(high)) and memory (CD44(high)CD45RB(low)) T cells, by flow cytometric analysis. Examination of spleen and peripheral blood o f C57BL/6 mice of various ages revealed that there was a reciprocal ag e-associated change in these two subpopulations, i.e. naive T cells pr edominant in young mice decreased with age, while memory T cells incre ased. In order to investigate the role of the thymus in the age change of naive and memory T cells, we employed two experimental systems: ra diation bone marrow chimeras constructed between young and old mice, a nd 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 refer ence to cytokine production by enriched naive and memory T cells, youn g naive T cells produced mainly IL-2 and young memory T cells mainly I L-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 low er than that of young mice. In addition, old naive T cells produced tw ice as much IL-4 than old memory T cells. These results suggested a di stinct age change in the profile of cytokine production and functional heterogeneity of two Th cell subpopulations.