Newly generated CD4 T cells in aged animals do not exhibit age-related defects in response to antigen.

Newly generated CD4 T cells in aged animals do not exhibit age-related defects in response to antigen.
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DOI:
10.1084/jem.20041933
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发表时间:
2005-03-21
影响因子:
15.3
通讯作者:
Swain, SL
Swain, SL
中科院分区:
医学1区
文献类型:
--
作者:
Haynes, L;Eaton, SM;Burns, EM;Randall, TD;Swain, SL

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利用T细胞受体转基因(TCRTG)小鼠模型,我们发现老年小鼠的TCRTGCD4细胞与年轻小鼠的细胞相比,保持了幼稚的表型,但对该抗原的增殖和IL-2产生减少。我们假设,与年龄相关的T细胞功能下降可能部分与T细胞的年龄有关。因为胸腺的输出量随着年龄的增长而减少,老年人的外周T细胞很可能比年轻人的年龄更大。为了研究这种可能性,我们操纵了年轻和老年小鼠外周血中CD4T细胞的年龄。新T细胞的产生是通过耗尽外周CD4T细胞或创造骨髓嵌合体来诱导的。在我们诱导产生新T细胞的年轻人和老年人中,这些新产生的细胞在体外和体内对抗原表现出强大的反应,表现出良好的增殖、IL-2产生和同源辅助功能。我们的结果表明,与年龄相关的缺陷对抗原刺激的反应,部分是由CD4T细胞的年龄引起的。
Using a T cell receptor transgenic (TCR Tg) mouse model, we have shown that TCR Tg CD4 cells from aged mice retain a naive phenotype, but exhibit reduced proliferation and IL-2 production in response to the antigen compared with cells from young mice. We hypothesize that age-related decreases in T cell function may be partly related to the age of the T cells. Because thymic output is decreased with age, peripheral T cells in older individuals are likely to be older than those in younger individuals. To investigate this possibility, we have manipulated the age of CD4 T cells in the periphery of young and aged mice. The production of new T cells was induced by depleting peripheral CD4 T cells or by creating bone marrow chimeras. In both young and aged individuals where we induced the production of new T cells, these newly generated cells exhibited robust responses to antigen ex vivo and in vivo, exhibiting good expansion, IL-2 production, and cognate helper function. Our results suggest that age-related defects in response to antigenic stimulation, in part, are caused by the age of the CD4 T cells.
胸腺和最近的胸腺移民在维持成年外周淋巴细胞库中的作用。
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