Antigenic experience dictates functional role of glycogen synthase kinase-3 in human CD4+ T cell responses.
Antigenic experience dictates functional role of glycogen synthase kinase-3 in human CD4+ T cell responses.
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DOI：
10.4049/jimmunol.181.12.8363
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发表时间：
2008-12-15
期刊：
影响因子：
--
通讯作者：
Martin M
中科院分区：
文献类型：
--
作者：
Garcia CA;Benakanakere MR;Alard P;Kosiewicz MM;Kinane DF;Martin M
由TCR和CD 28共刺激途径诱导的信号已显示导致组成型活性酶糖原合成酶激酶-3（GSK 3）的失活，所述糖原合成酶激酶-3（GSK 3）已涉及IL-2和T细胞增殖的调节。然而，目前尚不清楚GSK 3是否在幼稚和记忆性CD 4 + T细胞应答中发挥类似的作用。在这里，我们证明了在人类幼稚和记忆CD 4 + T细胞的增殖反应中对GSK 3失活的依赖性的分歧。我们发现，虽然CD 28共刺激增加了TCR刺激的幼稚和记忆CD 4 + T细胞中磷酸化GSK 3失活的频率，但记忆细胞的增殖反应较少依赖于GSK 3失活。相反，我们发现GSK 3 β在人类记忆性CD 4 + T细胞选择性调节IL-10回忆应答中起着以前未被认识的作用。此外，GSK 3 β失活的记忆性CD 4 + T细胞获得了以IL-10依赖性、细胞接触非依赖性方式抑制CD 4 + T细胞旁观者增殖的能力。我们的研究结果揭示了不同的人CD 4 + T细胞群体中GSK 3的功能存在二分法。
Signals induced by the TCR and CD28 costimulatory pathway have been shown to lead to the inactivation of the constitutively active enzyme, glycogen synthase kinase-3 (GSK3), which has been implicated in the regulation of IL-2 and T cell proliferation. However, it is unknown whether GSK3 plays a similar role in naive and memory CD4+ T cell responses. Here we demonstrate a divergence in the dependency on the inactivation of GSK3 in the proliferative responses of human naive and memory CD4+ T cells. We find that although CD28 costimulation increases the frequency of phospho-GSK3 inactivation in TCR-stimulated naive and memory CD4+ T cells, memory cells are less reliant on GSK3 inactivation for their proliferative responses. Rather we find that GSK3β plays a previously unrecognized role in the selective regulation of the IL-10 recall response by human memory CD4+ T cells. Furthermore, GSK3β-inactivated memory CD4+ T cells acquired the capacity to suppress the bystander proliferation of CD4+ T cells in an IL-10-dependent, cell contact-independent manner. Our findings reveal a dichotomy present in the function of GSK3 in distinct human CD4+ T cell populations.
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影响因子：
15.3
作者：
Ohteki, T;Parsons, M;Zakarian, A;Jones, R G;Nguyen, L T;Woodgett, J R;Ohashi, P S
通讯作者：
Ohashi, P S
影响因子：
4.4
作者：
Martin, M;Schifferle, RE;Michalek, SM
通讯作者：
Michalek, SM
DOI：
10.1073/pnas.0706409104
发表时间：
2007-11-20
影响因子：
11.1
作者：
Maier, Lisa M.;Anderson, David E.;Hafler, David A.
通讯作者：
Hafler, David A.
影响因子：
20.3
作者：
Rodionova, Elena;Conzelmann, Michael;Luft, Thomas
通讯作者：
Luft, Thomas
DOI：
10.1073/pnas.0603107103
发表时间：
2006-08-29
影响因子：
11.1
作者：
Ito, Tomoki;Wang, Yui-Hsi;Liu, Yong-Jun
通讯作者：
Liu, Yong-Jun