Tsukamoto Hirotake, Clise-Dwyer Karen, Huston Gail E, Duso Debra K, Buck Amanda L, Johnson Lawrence L, Haynes Laura, Swain Susan L
Trudeau Institute, Saranac Lake, NY 12983, USA.
Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18333-8. doi: 10.1073/pnas.0910139106. Epub 2009 Oct 8.
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.
随着年龄增长，胸腺产生的T细胞数量大幅减少，但即便在老年动物体内，仍能维持相当数量的初始T细胞库，这表明初始T细胞要么存活时间更长，要么更新速度更快，以维持T细胞的稳态。我们发现，随着年龄增长，初始CD4 T细胞的寿命逐渐延长。它们较长的寿命并不依赖于对自身肽/MHC II类分子的识别。源自老年干细胞的新产生的初始T细胞寿命较短，与年轻初始T细胞类似。相反，源自中年胸腺切除小鼠的初始CD4 T细胞在体内寿命更长，且其功能缺陷的发展加速。这些观察结果表明，初始T细胞在外周停留期间寿命变长。初始CD4 T细胞寿命的延长与促凋亡分子Bim表达的降低密切相关。我们认为，寿命的内在延长有助于维持初始T细胞的稳态，但会促进小鼠功能缺陷的发展。
