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

A Lerner, T Yamada, RA Miller - European journal of …, 1989 - Wiley Online Library
A Lerner, T Yamada, RA Miller
European journal of immunology, 1989Wiley Online Library
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 …
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‐1hi 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‐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.
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