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 human 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-1hiCD4+ 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-1hi phenotype. By limiting dilution methods, the frequency of concanavalin A-responsive T cells was found to be significantly reduced in the Pgp-1hi cell pool, whether measured by interleukin 2-dependent proliferation, interleukin 2 production or generation of cytotoxic effectors. Pgp-1hi and Pgp-1lo 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-1hi T cells, and also to lower responsiveness of cells in the Pgp-1hi subset.