Inflammatory chemokine receptors regulate CD8(+) T cell contraction and memory generation following infection.
Inflammatory chemokine receptors regulate CD8(+) T cell contraction and memory generation following infection.
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DOI：
10.1084/jem.20102110
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发表时间：
2011-08-01
期刊：
影响因子：
--
通讯作者：
Woodland DL
中科院分区：
文献类型：
--
作者：
Kohlmeier JE;Reiley WW;Perona-Wright G;Freeman ML;Yager EJ;Connor LM;Brincks EL;Cookenham T;Roberts AD;Burkum CE;Sell S;Winslow GM;Blackman MA;Mohrs M;Woodland DL
缺乏CXCR3和CCR5表达的CD8+T细胞在病毒感染后收缩受损，并产生更多的记忆细胞。T细胞激活和分化过程中接收到的分子信号影响着T细胞从幼稚前体细胞到记忆的发展。在这项研究中，我们描述了趋化因子受体CCR5和CXCR3在流感病毒感染后调节效应器CD8+T细胞收缩和记忆生成中的新作用。我们发现，CCR5CDXCR3CD8细胞在病毒清除后收缩明显减少，导致大量−/−+T细胞的记忆建立。CCR5−/−CXCR3−/−细胞在感染高峰期肺组织中CD69的表达降低，这与其分化定位和记忆前体细胞的迅速出现相一致。对单个趋化因子受体缺陷细胞的分析表明，CXCR3是这种表型的主要原因，尽管CCR5也在增强T细胞记忆方面发挥了作用。加入外源性抗原可逆转CCR5CXCR3CXCR3−/−−/−细胞的表型，使其激活和收缩。在慢性结核分枝杆菌感染中也观察到了类似的结果。总之，这些数据支持记忆CD8+T细胞生成的模型，在该模型中，T细胞在感染组织中的趋化因子定向定位调节抗原相遇并控制CD8+T细胞激活和分化的程度，最终调节效应者与记忆细胞的命运决定。
CD8+ T cells lacking CXCR3 and CCR5 expression have impaired contraction and generate an increased number of memory cells after virus infection. The development of T cell memory from naive precursors is influenced by molecular cues received during T cell activation and differentiation. In this study, we describe a novel role for the chemokine receptors CCR5 and CXCR3 in regulating effector CD8+ T cell contraction and memory generation after influenza virus infection. We find that Ccr5−/− Cxcr3−/− cells show markedly decreased contraction after viral clearance, leading to the establishment of massive numbers of memory CD8+ T cells. Ccr5−/− Cxcr3−/− cells show reduced expression of CD69 in the lung during the peak of infection, which coincides with differential localization and the rapid appearance of memory precursor cells. Analysis of single chemokine receptor–deficient cells revealed that CXCR3 is primarily responsible for this phenotype, although there is also a role for CCR5 in the enhancement of T cell memory. The phenotype could be reversed by adding exogenous antigen, resulting in the activation and contraction of Ccr5−/− Cxcr3−/− cells. Similar results were observed during chronic Mycobacterium tuberculosis infection. Together, the data support a model of memory CD8+ T cell generation in which the chemokine-directed localization of T cells within infected tissues regulates antigen encounter and controls the extent of CD8+ T cell activation and differentiation, which ultimately regulates effector versus memory cell fate decisions.
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激活表型，而不是中心或效应子内存表型，可预测记忆CD8+ T细胞的回忆功效。
影响因子：
15.3
作者：
Hikono, Hirokazu;Kohlmeier, Jacob E.;Takamura, Shiki;Wittmer, Susan T.;Roberts, Alan D.;Woodland, David L.
通讯作者：
Woodland, David L.
影响因子：
5.4
作者：
Fadell, Shaza A.;Bromley, Shannon K.;Medoff, Benjamin D.;Luster, Andrew D.
通讯作者：
Luster, Andrew D.
影响因子：
30.5
作者：
Kaech, SM;Tan, JT;Ahmed, R
通讯作者：
Ahmed, R
影响因子：
82.9
作者：
Badovinac, VP;Messingham, KAN;Harty, JT
通讯作者：
Harty, JT
影响因子：
6.2
作者：
Akashi, S;Sho, M;Nakajima, Y
通讯作者：
Nakajima, Y