Pgp‐1hi T lymphocytes accumulate with age in mice and respond poorly to concanavalin A

Abstract

Aging is associated with an accumulation of T cells functionally hyporesponsive to the effects of mitogens such as concanavalin A. Recent studies in mice and humans have identified surface markers useful for distinguishing antigen‐stimulated memory T cells from virgin T cells. In mice, memory T cells within the CD8+ cell population have been shown to express relatively high levels of the cell surface glycoprotein Pgp‐1. On the theory that aging might diminish the supply of virgin thymic emigrants without compromising the production of memory T cells, we examined the proportion of Pgp‐1 hi CD4+ and CD8+ cells in the spleen, blood and lymph nodes of mice of varying age. We found a dramatic (2.5‐fold) age‐associated increase in the percentage of cells with the Pgp‐1 hi phenotype. By limiting dilution methods, the frequency of concanavalin A‐responsive T cells was found to be significantly reduced in the Pgp‐1 hi cell pool, whether measured by interleukin 2‐dependent proliferation, interleukin 2 production or generation of cytotoxic effectors. Pgp‐1 hi and Pgp‐1 lo T cells from young mice proliferate equally well when stimulated by optimal doses of phorbol myristate acetate and ionomycin suggesting that the poor responses to concanavalin A do not simply reflect low viability. Aging leads both to an increase in mitogen‐hyporesponsive Pgp‐1 hi T cells, and also to lower responsiveness of cells in the Pgp‐1 hi subset.