Human CD4+ T cell recent thymic emigrants are identified by protein tyrosine kinase 7 and have reduced immune function.
Human CD4+ T cell recent thymic emigrants are identified by protein tyrosine kinase 7 and have reduced immune function.
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DOI：
10.1084/jem.20080996
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发表时间：
2009-02-16
期刊：
影响因子：
--
通讯作者：
Lewis DB
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文献类型：
--
作者：
Haines CJ;Giffon TD;Lu LS;Lu X;Tessier-Lavigne M;Ross DT;Lewis DB
CD 4+近期胸腺移出物（RTE）包括临床和免疫学上重要的T细胞群体，其指示胸腺输出，并且对于维持初始CD 4 + T细胞区室的多样性αβ-T细胞受体（TCR）库是必需的。然而，它们的频率和功能知之甚少，因为没有已知的表面标志物将它们与较老的非RTE幼稚CD 4 + T细胞区分开来。我们证明，蛋白酪氨酸激酶7（PTK 7）是一种新的人类CD 4 + RTEs的标志物。与其最近的胸腺起源一致，与PTK 7-naive CD 4 + T细胞相比，人PTK 7 + RTEs含有更高水平的信号联合TCR基因切除环，对白细胞介素（IL）-7的反应更强，并且在完全胸腺切除术后迅速下降。重要的是，在αβ-TCR/CD 3和CD 28结合后，CD 4 + RTE比PTK 7 − naive CD 4 + T细胞增殖更少，产生更少的IL-2和干扰素-γ。CD 4 + RTE效应器功能的不成熟可能导致在CD 4 + RTE占主导地位的情况下（例如胎儿和新生儿或免疫重建后）观察到的CD 4 + T细胞免疫力下降。通过PTK 7染色鉴定存活的CD 4 + RTEs的能力对于监测健康个体和遗传性或获得性CD 4 + T细胞免疫缺陷患者的胸腺输出是有用的。
CD4+ recent thymic emigrants (RTEs) comprise a clinically and immunologically important T cell population that indicates thymic output and that is essential for maintaining a diverse αβ–T cell receptor (TCR) repertoire of the naive CD4+ T cell compartment. However, their frequency and function are poorly understood because no known surface markers distinguish them from older non-RTE naive CD4+ T cells. We demonstrate that protein tyrosine kinase 7 (PTK7) is a novel marker for human CD4+ RTEs. Consistent with their recent thymic origin, human PTK7+ RTEs contained higher levels of signal joint TCR gene excision circles and were more responsive to interleukin (IL)-7 compared with PTK7− naive CD4+ T cells, and rapidly decreased after complete thymectomy. Importantly, CD4+ RTEs proliferated less and produced less IL-2 and interferon-γ than PTK7− naive CD4+ T cells after αβ-TCR/CD3 and CD28 engagement. This immaturity in CD4+ RTE effector function may contribute to the reduced CD4+ T cell immunity observed in contexts in which CD4+ RTEs predominate, such as in the fetus and neonate or after immune reconstitution. The ability to identify viable CD4+ RTEs by PTK7 staining should be useful for monitoring thymic output in both healthy individuals and in patients with genetic or acquired CD4+ T cell immunodeficiencies.
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影响因子：
15.3
作者：
Kimmig, Sonja;Przybylski, Grzegorz K;Schmidt, Christian A;Laurisch, Katja;Mowes, Beate;Radbruch, Andreas;Thiel, Andreas
通讯作者：
Thiel, Andreas
影响因子：
64.8
作者：
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通讯作者：
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影响因子：
15.3
作者：
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通讯作者：
WALLER, EK
影响因子：
4.4
作者：
Cleary, AM;Tu, WW;Lewis, DB
通讯作者：
Lewis, DB