Developmental pathways of cortical and medullary thymocytes in aging

This study was designed to determine the stage of T cell development that is refractory to thymic effect in aging. Thymocytes from young (3 months) and old (24 months) mice (C57BL/6J, Thy1.2), separated into cortical (peanut agglutinin plus, PNA+) and medullary (PNA-) subpopulations, as well as unseparated cells, were seeded onto lymphoid-depleted fetal thymus (FT) explants (C57BL/Ka, Thy1.1). The patterns of T cell development were subsequently examined during 11 days of culture. In cultures containing PNA+ or unseparated thymocytes of the young, values of double positive (CD4+CD8+, DP) cells were minimal during the first week, and an increase was noted thereafter, whereas in the old, the DP values increased gradually from onset of culture. The PNA- cells of the young gave rise to an initial peak level of CD4+CD8- on day 5, which was not detected in the old. By the eleventh day of culture, significantly lower percents of DP and increased double negative (CD4-CD8-, DN) and CD4-CD8+ phenotypes were observed in the old as compared with young donor-derived cells. The proportion of cells expressing IL-2R and TCRαβ and TCRγδ among the different CD4/CD8 subsets was similar in both age groups. Since the ultimate development of the cells from young and old donors was in a fetal thymus, we conclude that the patterns of thymocyte development are determined at an early stage of residence in the original donor thymus.