Age-related dysregulation in CD8 T cell homeostasis: Kinetics of a diversity loss
Age-related dysregulation in CD8 T cell homeostasis: Kinetics of a diversity loss
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DOI：
10.4049/jimmunol.165.5.2367
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发表时间：
2000-09-01
影响因子：
4.4
通讯作者：
Nikolich-Zugich, J
中科院分区：
文献类型：
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作者：
LeMaoult, J;Messaoudi, I;Nikolich-Zugich, J
携带不同TCR V β家族的外周T细胞的相对多样性和代表性在出生和成年晚期之间受到非常严格的调节。相比之下，个体老年人和C3H.SW和B10.BR老年小鼠在这种调节中显示出剧烈的破坏。本文研究了老年C57 BL/6（B6）小鼠T细胞群稳态失调的动力学。使用单克隆抗体染色，我们发现携带不同TCRV β元件的α β（+）CD 8（+）或CD 4（+）T细胞的百分比在12月龄的小鼠中几乎保持不变。然而，在22月龄小鼠中，由于CD 8（+）TCE的出现，这种模式受到了严重的干扰。扩增的T细胞在VP使用中没有显示出任何明显的偏倚，并且在迄今为止检查的所有情况下都来自单个克隆。与B细胞克隆扩增相比，TCE在生命后期出现。然而，与在人类中检测到的TCE相反，TCE通常不稳定，在2-4个月内消失，其他TCE在同一时间范围内出现。对胸腺T细胞、胸腺切除小鼠、酸性幼T细胞转移到Rag 1（-/-）小鼠中进行的其他研究表明，克隆扩增发生在外周，并且它们的发生因胸腺输出和/或功能降低而加速。
Relative diversity and representation of peripheral T cells bearing different TCR V beta families are remarkably tightly regulated between birth and advanced adulthood. By contrast, individual elderly humans and C3H.SW and B10.BR aged mice display drastic disruption in such regulation. It was suggested that the alterations in the murine aged T cell compartment were due to age-related clonal T cell expansions (TCE), Here, we studied the kinetics of homeostatic dysregulation of T cell populations in aged C57BL/6 (B6) mice. Using mAb staining, we show that the percentages of alpha beta (+)CD8(+) or CD4(+) T cells bearing different TCRV beta elements remain virtually constant in mice up to 12 mo of age. In 22-mo-old mice, however, there is a dramatic disturbance of this pattern owing to the emergence of CD8(+) TCE, Expanded T cells did not show any obvious bias in VP usage and were derived in all cases examined thus far from a single clone, TCE appeared later in life, compared with B cell clonal expansions. However, and in contrast to those detected in humans, TCE were frequently unstable disappearing within 2-4 mo, with other TCE appearing within the same time frame. Additional studies carried on thymic T cells, thymectomized mice, acid young T transferred cells into Rag1(-/-) mice suggest that the clonal expansions occur in the periphery and that their onset is accelerated by decreased thymic output and/or function(s).