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 CD44hi. 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.
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Department of Immunology, Sidney Kimmel Cancer Center, San Diego, CA 92121, USA.
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D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D016026:Bone Marrow Transplantation; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002678:Chimera; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010641:Phenotype; D012038:Regeneration
D016207:Cytokines