Maturation of CD4(+) lymphocytes in the aged microenvironment results in amemory-enriched population

With advancing age the CD4(+) T lymphocyte compartment becomes enriched for memory cells in both humans and experimental animals, Although it has been assumed that the shift from a naive to a memory-dominant population is due to a lifetime of antigenic exposure and selection as well as a loss of nai ve cell input due to reduced thymopoiesis, the present data suggest that th e aged microenvironment influences the maturation of newly produced CD4(+) T cells. In two models, aged and young mice were compared for the ability t o reconstitute their peripheral CD4(+) T cell pools following depletion, an d both age groups were found to be competent to renew this population. Howe ver, the phenotype and lymphokine profile of populations arising in aged an imals were distinctly different from those in the young mice. In contrast t o the expectation that depletion and reconstitution might give rise to a na ive-dominant T cell pool, aged mice reconstituted a population nearly indis tinguishable from that found in control age-matched individuals, The majori ty of the CD4(+) pool were CD44(high) CD45RB(low) Mel-14(low) and upon acti vation with anti-CD3 these CD4(+) T cells produced mRNA for IL-2, IL-4, IL- 5, and IFN-gamma, In aged bone marrow-transplanted mice, the same phenotypi c profile and cytokine mRNA pattern were found in CD4(+) T cells of host an d donor origin. In contrast, the majority of CD4(+) T cells in young recons tituted mice were CD44(low) CD45RB(high) Mel-14(high). These lymphocytes, w hen activated, produced high levels of mRNA for IL-2, with little or no IL- 4, IL-5, or IFN-gamma mRNA.