Mechanisms of age-related decline in antigen-specific T cell proliferative response: IL-2 receptor expression and recombinant IL-2 induced proliferative response of purified tac-positive T cells

Abstract

Proliferative response of T cells from aged persons was significantly reduced to a specific antigen tuberculin-active peptide (TAP) determined by [ 3H]TdR uptake and FCM in comparison to that from the young. Cytokinetic analysis for the proliferative response to TAP showed that, in the aged, the clonal size or the number of the first generation responding cells to TAP was not significantly reduced but the ability to repeat replication was more profoundly affected. Neither the delayed entry into the cell replication nor prolongation of the cell cycle time could explain these results. Similar results have been reported on the proliferative response of T cells to mitogen: PHA (Phytohemagglutinin). Expression of Tac-antigen on T cells determined by anti-Tac antibody binding with FACS after stimulation with either TAP or PHA was found to be reduced significantly in the aged. Both the numbers of high and low affinity IL-2 receptors determined by radiolabelled IL-2 binding assay were also reduced in the aged, but the degree of reduction in number of high affinity ones was more pronounced than that in low affinity ones. Tac-positive T cells were isolated with the use of anti-Tac rosette methods and stimulated with recombinant IL-2 (r-IL-2). Their proliferative response was significantly lower in the aged than that in the young at any concentration of r-IL-2 examined. The number of the first generation responding cells to r-IL-2 in purified Tac-positive T cells from the aged was 82% of that from the young whereas the proliferative response by aged T cells was 39% of that by young ones when the cells were allowed to repeat replication for 3 days. The mechanisms of these multifactorial defects in proliferation of T cells from aged persons were discussed.