Cytokine production by subsets of CD4 memory T cells differing in P-glycoprotein expression: effects of aging

We have shown previously that the mouse CD4 memory cell subset can be divided into two subpopulations based on differential expression of P-glycoprotein. Cells with high levels of P-glycoprotein can be detected by extrusion of the fluorochrome Rhodamine 123; they are referred to as R123lo cells. These R123lo T cells increase with age and have been shown not to respond to anti-CD3 and IL-2 by proliferation or IL-4 production. We report here (a) that the failure of the R123lo CD4 memory population to respond to anti-CD3/IL-2 stimulation cannot be overcome by addition of anti-CD28, PMA, IL-4 or IL-12, alone or in various combinations, and (b) that this age-dependent subset exhibits impaired production of IL-5 and IL-10 as well as decreased proliferation. R123lo CD4 memory cells from young mice are also deficient in IFN gamma secretion by this subset. Although the R123lo cells respond poorly to receptor-dependent agonists, they can be triggered to proliferate and produce IFN gamma by the combination of PMA and ionomycin. In addition to increasing the proportion of R123lo cells in the memory CD4 pool, aging also leads to a decline in the ability of R123hi cells to produce IL-5 and IL-10. Thus, the accumulation of R123lo cells cannot by itself account for the poor proliferation and Th2 cytokine production of aged T cells in cytokine-supplemented culture conditions.