The impact of aging on memory T cell phenotype and function in the human bone marrow.
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.
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, 6020 Innsbruck, Austria. dietmar.herndler-brandstetter@yale.edu
Dietmar
D
Herndler-Brandstetter
Katja
K
Landgraf
Alexandar
A
Tzankov
Brigitte
B
Jenewein
Regina
R
Brunauer
Gerhard T
GT
Laschober
Walther
W
Parson
Frank
F
Kloss
Robert
R
Gassner
Günter
G
Lepperdinger
Beatrix
B
Grubeck-Loebenstein
D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001853:Bone Marrow / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D007156:Immunologic Memory; D015759:Ionomycin / Q000494:pharmacology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate