Aging affects the regeneration of the CD8+ T cell compartment in bone marrow transplanted mice

A chimeric mouse model has been used to determine the effect of aging on the differentiation of CD8(+) T cells and on the regeneration capacity of the mature peripheral T cell pool after radiation induced depletion. Bone marrow cells from Thy 1.1(+) mice were transplanted into lethally irradiated young or aged mice (Thy 1.2(+)). After 6 weeks, splenic CD8(+) T cells were subjected to phenotypic and functional examinations by flow cytometry. Both young and aged mice were able to develop donor derived (Thy 1.1(+)) CD8(+) T cells. Although the absolute number of T cells was reduced in aged recipients, the ratio of CD4(+) to CD8(+) T cells of donor-origin was the same in young Thy 1.1(+) control mice as it was in both young and aged chimeric mice, indicating that aging has no effect on the ratio of CD4(+) to CD8(+) T cells produced by the thymus. However, the percentage of CD8(+) cells in the total Thy 1.2(+) (host-origin)T cell population was significantly higher in young chimeric mice than in age-matched Thy 1.2(+) control mice (P < 0.01), suggesting that a significant over expansion of the Thy 1.2(+) CD8(+) subset occurred in young mice during regeneration. The Thy 1.1(+) CD8(+) T cells that developed in young hosts were of a naive phenotype with a majority of cells expressing a low level of CD44. In contrast, the majority of those that developed in the aged host displayed a memory phenotype with a high percentage of cells being CD44(hi). In addition, the production of IL-4 and IFN-gamma by Thy 1.1(+) CD8(+) T cells was affected by the age of the host. A greater fraction of aged Thy 1.1(+) CD8(+) T cells could be induced to produce either IFN-gamma or IL-4 than young CD8(+) T cells. These results suggested that the aged microenvironment has a significant effect on newly developed CD8(+) T cells and that the age of the microenvironment also influences the regeneration capacity of CD8(+) T cells. (C) 2000 Published by Elsevier Science Ireland Ltd. AII rights reserved.