The basis of distinctive IL-2- and IL-15-dependent signaling: weak CD122-dependent signaling favors CD8+ T central-memory cell survival but not T effector-memory cell development.
The basis of distinctive IL-2- and IL-15-dependent signaling: weak CD122-dependent signaling favors CD8+ T central-memory cell survival but not T effector-memory cell development.
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DOI：
10.4049/jimmunol.1003961
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发表时间：
2011-11-15
期刊：
影响因子：
--
通讯作者：
Malek TR
中科院分区：
文献类型：
--
作者：
Castro I;Yu A;Dee MJ;Malek TR
最近的研究表明，IL-2 和 IL-15 通过共同受体亚基诱导不同水平的信号传导，并且这种不同的信号传导指导抗原激活的 CD8+ T 细胞的命运。在这里，我们直接检查了 IL-2 和 IL-15 的近端信号传导以及 CD8+ T 细胞的初级和记忆反应，这是各种 CD122 依赖性信号传导的结果。最初，IL-2 和 IL-15 诱导类似的 pStat5 和 pS6 激活，但这些活性仅由 IL-2 维持。短暂的 IL-15 依赖性信号传导是由于 IL-15Rα 的表达有限所致。为了研究体内不同 CD122 信号传导对 CD8+ T 细胞反应的结果，使用小鼠模型中的 OT-I T 细胞，其中 CD122 信号因 CD122 胞质尾部内的突变而减弱，或者在缺乏 CD122 表达的情况下由转基因 Bcl-2 提供内在生存功能。在缺乏 CD122 信号传导的情况下，通常会发生正常的初级反应，但未维持引发的 CD8+ T 细胞。与此形成鲜明对比的是，微弱的 CD122 信号传导支持 TCM 细胞的发育和存活，但不支持 TEM 细胞。 CD122−/− CD8+ T 细胞中 Bcl-2 的转基因表达也支持 TCM 细胞的存活和持久性，但不能挽救 TEM 发育。这些数据表明，微弱的 CD122 信号很容易通过提供生存信号来支持中医发展。然而，TEM 开发需要独立于 Bcl-2 的更强信号。我们的研究结果与低、中、高 CD122 信号传导分别支持中医记忆存活、TEM 编程和终末 TEFF 分化的模型一致。
Recent work suggests that IL-2 and IL-15 induce distinctive levels of signaling through common receptor subunits and that such varied signaling directs the fate of antigen-activated CD8+ T cells. Here we directly examined proximal signaling by IL-2 and IL-15 and CD8+ T cell primary and memory responses as a consequence of varied CD122-dependent signaling. Initially, IL-2 and IL-15 induced similar pStat5 and pS6 activation, but these activities were only sustained by IL-2. Transient IL-15-dependent signaling is due to limited expression of IL-15Rα. To investigate the outcome of varied CD122 signaling for CD8+ T cell responses in vivo, OT-I T cells were utilized from mouse models where CD122 signals were attenuated by mutations within the cytoplasmic tail of CD122 or intrinsic survival function was provided in the absence of CD122 expression by transgenic Bcl-2. In the absence of CD122 signaling, generally normal primary response occurred, but the primed CD8+ T cells were not maintained. In marked contrast, weak CD122 signaling supported development and survival of TCM but not TEM cells. Transgenic expression of Bcl-2 in CD122−/− CD8+ T cells also supported the survival and persistence of TCM cells but did not rescue TEM development. These data indicate that weak CD122 signals readily support TCM development largely through providing survival signals. However, stronger signals, independent of Bcl-2, are required for TEM development. Our findings are consistent with a model whereby low, intermediate, and high CD122 signaling support TCM memory survival, TEM programming, and terminal TEFF differentiation, respectively.
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影响因子：
15.9
作者：
Manjunath, N;Shankar, P;von Andrian, UH
通讯作者：
von Andrian, UH
影响因子：
7.8
作者：
HEMAR, A;SUBTIL, A;LIEB, M;MORELON, E;HELLIO, R;DAUTRYVARSAT, A
通讯作者：
DAUTRYVARSAT, A
影响因子：
64.8
作者：
Araki, Koichi;Turner, Alexandra P.;Shaffer, Virginia Oliva;Gangappa, Shivaprakash;Keller, Susanne A.;Bachmann, Martin F.;Larsen, Christian P.;Ahmed, Rafi
通讯作者：
Ahmed, Rafi
DOI：
10.1084/jem.191.5.771
发表时间：
2000-03-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kennedy MK;Glaccum M;Brown SN;Butz EA;Viney JL;Embers M;Matsuki N;Charrier K;Sedger L;Willis CR;Brasel K;Morrissey PJ;Stocking K;Schuh JC;Joyce S;Peschon JJ
通讯作者：
Peschon JJ
影响因子：
32.4
作者：
Kallies, Axel;Xin, Annie;Nutt, Stephen L.
通讯作者：
Nutt, Stephen L.