The impact of aging on memory T cell phenotype and function in the human bone marrow.
J Leukoc Biol, 2012/2;91(2):197-205.
Herndler-Brandstetter D[1], Landgraf K, Tzankov A, Jenewein B, Brunauer R, Laschober GT, Parson W, Kloss F, Gassner R, Lepperdinger G, Grubeck-Loebenstein B
Affiliations
PMID: 22013229DOI: 10.1189/jlb.0611299
Impact factor: 6.011
Abstract
Recently, the BM has been shown to play a key role in regulating the survival and function of memory T cells. However, the impact of aging on these processes has not yet been studied. We demonstrate that the number of CD4⁺ and CD8⁺ T cells in the BM is maintained during aging. However, the composition of the T cell pool in the aged BM is altered with a decline of naïve and an increase in T(EM) cells. In contrast to the PB, a highly activated CD8⁺CD28⁻ T cell population, which lacks the late differentiation marker CD57, accumulates in the BM of elderly persons. IL-6 and IL-15, which are both increased in the aged BM, efficiently induce the activation, proliferation, and differentiation of CD8⁺ T cells in vitro, highlighting a role of these cytokines in the age-dependent accumulation of highly activated CD8⁺CD28⁻ T cells in the BM. Yet, these age-related changes do not impair the maintenance of a high number of polyfunctional memory CD4⁺ and CD8⁺ T cells in the BM of elderly persons. In summary, aging leads to the accumulation of a highly activated CD8⁺CD28⁻ T cell population in the BM, which is driven by the age-related increase of IL-6 and IL-15. Despite these changes, the aged BM is a rich source of polyfunctional memory T cells and may thus represent an important line of defense to fight recurrent infections in old age.
MeSH terms
Adult; Aged; Aging; Antigens, Differentiation, T-Lymphocyte; Bone Marrow; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cells, Cultured; Cytokines; Female; Gene Rearrangement, T-Lymphocyte; Humans; Immunologic Memory; Ionomycin; Lymphocyte Count; Male; Middle Aged; T-Lymphocyte Subsets; Tetradecanoylphorbol Acetate
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