Age-associated increase in lifespan of naive CD4 T cells contributes to T-cell homeostasis but facilitates development of functional defects.
With age, T-cell generation from the thymus is much reduced, yet a substantial naïve T-cell pool is maintained even in aged animals, suggesting that naïve T cells either persist longer or turn over faster to maintain T-cell homeostasis. We found that with age, naïve CD4 T cells became progressively longer-lived. Their longer lifespan did not depend on recognition of self-peptide/class II. Newly generated naïve T cells derived from aged stem cells had a shorter lifespan, like that of young naïve T cells. Conversely, naïve CD4 T cells derived from middle-aged thymectomized mice were longer-lived in vivo, and their development of functional defects was accelerated. These observations suggest that naïve T cells develop their longer lifespan during their sojourn in the periphery. Increased longevity of naïve CD4 T cells correlated well with reduced expression of proapoptotic molecule Bim. We suggest that the intrinsic increase in longevity helps maintain naïve T-cell homeostasis but facilitates the development of functional defects in mice.
Tsukamoto
Hirotake
H
Trudeau Institute, Saranac Lake, NY 12983, USA.
Clise-Dwyer
Karen
K
Huston
Gail E
GE
Duso
Debra K
DK
Buck
Amanda L
AL
Johnson
Lawrence L
LL
Haynes
Laura
L
Swain
Susan L
SL
D000375:Aging; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002470:Cell Survival; D006649:Histocompatibility Antigens / Q000276:immunology; D006706:Homeostasis; D007113:Immunity, Innate; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013934:Thymectomy
D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D006649:Histocompatibility Antigens; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell