Bim dictates naive CD4 T cell lifespan and the development of age-associated functional defects.
Bim dictates naive CD4 T cell lifespan and the development of age-associated functional defects.
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DOI：
10.4049/jimmunol.1001668
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发表时间：
2010-10-15
期刊：
影响因子：
--
通讯作者：
Swain SL
中科院分区：
文献类型：
--
作者：
Tsukamoto H;Huston GE;Dibble J;Duso DK;Swain SL
随着年龄的增长，外周幼稚的CD4T细胞变得更长寿和功能受损，它们表达的Bim水平降低，Bim是一种促凋亡的Bcl家族成员。在这项研究中，我们证明了幼稚的CD4T细胞减少了Bim的表达，内在地调节了它们在外周的更长寿命。此外，使用由Bim+/+和Bim+/−骨髓细胞重组的混合骨髓嵌合体，Bim+/−初始CD4T细胞表现出加速发展的年龄相关功能障碍，包括增殖和IL-2产生减少以及B细胞辅助功能缺陷，而其周转率没有任何增加。然而，新产生的Bim+/−幼稚CD4T细胞在中年小鼠中并没有缺陷，这表明它们在外周持续存在的额外要求。这些与年龄相关的免疫缺陷独立于“老化”的宿主环境发展，没有广泛的分裂，区别于经典的“衰老”。我们认为，随着年龄的增长，幼稚的CD4T细胞中Bim水平的降低是导致细胞寿命延长和与年龄相关的功能缺陷发生的起始步骤。
With age peripheral naïve CD4 T cells become both longer-lived and functionally impaired and they express reduced levels of Bim, a pro-apoptotic Bcl-family member. In this study, we show that reduced Bim expression by naïve CD4 T cells intrinsically mediates their longer lifespan in the periphery. Moreover, using mixed bone marrow chimeras reconstituted with Bim+/+ and Bim+/− bone marrow cells, Bim+/− naïve CD4 T cells exhibit accelerated development of age-associated dysfunctions including reduced proliferation and IL-2 production and defective helper function for B cells, without any increase in their turnover. However, newly generated Bim+/− naïve CD4 T cells in middle aged mice are not defective, indicating an additional requirement for their persistence in the periphery. These age-associated immune defects develop independently of the “aged” host environment and without extensive division, distinguishing them from classic “senescence”. We suggest that the reduction of Bim levels with age in naïve CD4 T cell is the initiating step that leads to increased cellular lifespan and development of age-associated functional defects.
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影响因子：
15.3
作者：
Haynes, L;Eaton, SM;Burns, EM;Randall, TD;Swain, SL
通讯作者：
Swain, SL
影响因子：
32.4
作者：
Hughes, Peter D.;Belz, Gabrielle T.;Fortner, Karen A.;Budd, Ralph C.;Strasser, Andreas;Bouillet, Philippe
通讯作者：
Bouillet, Philippe
影响因子：
4.4
作者：
Kilpatrick, Ryan D.;Rickabaugh, Tammy;Jamieson, Beth D.
通讯作者：
Jamieson, Beth D.
影响因子：
4.4
作者：
Garcia, GG;Miller, RA
通讯作者：
Miller, RA
影响因子：
64.8
作者：
Janzen, Viktor;Forkert, Randolf;Scadden, David T.
通讯作者：
Scadden, David T.