The role of T cell phenotypes in decreased lymphoproliferation of the elderly.

A possible mechanism of the decreased mitogen-induced lymphoproliferation of the elderly is a shift in the relative numbers of T lymphocyte subpopulations. Results from studies examining such changes have been conflicting. In an effort to resolve this conflict, alterations in T cell subsets in the peripheral blood of a large number of relatively healthy, elderly subjects (149; mean age 84.6) were evaluated. Although there were several differences in percentages of subpopulations between elderly and young subjects, no significant differences in the absolute numbers of lymphocytes, monocytes, or T cell subsets between the groups were observed. In addition, there was no correlation between mitogen-induced lymphoproliferation and T cell subsets. Since the decreased mitogen response could reflect a difference in the ability of one T cell subset to proliferate, the phenotype of the T cells after stimulation with PHA was determined. Although the elderly demonstrated a decreased number of all T cell subsets after PHA stimulation compared to young subjects, the most pronounced decrease was in CD8+ cells. Further, young individuals demonstrated a significant increase in the percentage of CD8+ cells (p less than 0.001) after 72 hr of culture with PHA; elderly subjects showed no change in the percentage of T cell subsets. Although both groups had an increase in interleukin 2 receptor (IL2R), transferrin receptor (TfR), and MHC class II Ag (HLA-DR) positive cells after PHA stimulation, the mean percentage of TfR+ cells was significantly greater in the young than in the elderly (p less than 0.05). This decreased expression of TfR+ cells in the elderly was reflected by a decreased percentage of CD8+ cells expressing TfR. In addition, the percentages of CD8+ cells, CD8+ cells expressing TfR, and CD8+ cells expressing IL2R after activation correlated with PHA-induced proliferation. These results suggest that the impaired lymphoproliferative ability of elderly cells is not related to the proportions of T cell subsets present in peripheral blood. Rather, there appears to be some defect in the ability of all T cells, but especially of the T suppressor/cytotoxic cells, of the elderly to respond to PHA manifested by a decreased expression of transferrin receptors.