Age-related changes of the function of T cell subsets: Predominant defect of the proliferative response in CD8 positive T cell subset in aged persons

Abstract

The proportion of CD8 positive cells in the peripheral blood AET-rosette forming T cells from aged persons was significantly reduced than that from young persons. The difference in the proportion between aged and young groups became more significant after proliferative response to a mitogen phytohemagglutinin (PHA) or a specific antigen tuberculin active peptide (TAP). The purified macrophage-deprived T cells (Twp), CD4 (T4) positive cells or CD8 positive cells were prepared from aged or young persons. These cell preparations lost proliferative response to PHA or TAP but showed marked proliferative response to the combined stimulation to 1 μM of ionomycin and 1 nM of phorbol-12-myristate-13-acetate (PMA) at usual culture cell density (2.5 × 10 5/ ml). Proliferative responses of these cell preparations to the combined stimulation were significantly reduced in the aged than those in the young and the magnitude of the difference in the proliferative responses between aged and young groups was more pronounced in CD8 positive cell population than in CD4 positive cell population. Although the cell preparations were relatively independent of exogenous IL-2 for the proliferative response to the combined stimulation of ionomycin and PMA at usual culture cell density, they needed exogenous IL-2 for sustained proliferation at lower culture cell density (5 × 10 3/ ml). These IL-2-dependent proliferative responses to the combined stimulation in the aged were significantly lower than those in the young and again the difference in the proliferative magnitude between aged and young groups was greater in CD8 positive population. The mechanism(s) of age-related change of the proportion and proliferative ability of T subsets were discussed.