CXCL12 mediates CCR7-independent homing of central memory cells, but not naive T cells, in peripheral lymph nodes.
CXCL12 mediates CCR7-independent homing of central memory cells, but not naive T cells, in peripheral lymph nodes.
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DOI：
10.1084/jem.20031645
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发表时间：
2004-04-19
期刊：
影响因子：
--
通讯作者：
Weninger W
中科院分区：
文献类型：
--
作者：
Scimone ML;Felbinger TW;Mazo IB;Stein JV;Von Andrian UH;Weninger W
与其他T细胞亚群相比，中央记忆CD8+T细胞具有更好的抗感染保护性免疫。中医的再循环主要通过次级淋巴器官，包括外周淋巴结(PLN)。在这里，我们报告了中医，不同于原始T细胞，可以CCR7依赖和非独立的方式来定位PLN。在次级淋巴器官中不表达CCR7配体的缺乏淋巴T细胞(PLT/PLT)小鼠的归巢实验表明，中医以野生型(WT)水平的∼20%迁移到PLN，而原始T细胞的归巢减少了95%。因此，PLT/PLT PLN中的大部分内源性CD8+T细胞表现为中医表型。活体显微镜下观察PLT/PLT髂下淋巴结发现，中药在高内皮微静脉(HEV)中卷曲并牢固地黏附(黏附)，而初始T细胞不能黏附。中药在PLT/PLT HEV中的黏附是百日咳毒素敏感的，并被抗CXCL12(SDF-1α)阻断。在WT动物中，抗CXCL12还将中医归巢到PLN的作用减少了20%，表明这种趋化因子在生理性CCR7激动剂存在的情况下发挥了非多余的作用。总之，这些数据区分了初始T细胞和Tcm细胞，只有Tcm细胞表现出更大的迁移灵活性，因为它们在归巢到PLN期间对CCR7配体和CXCL12都有更高的反应性。
Central memory CD8+ T cells (TCM) confer superior protective immunity against infections compared with other T cell subsets. TCM recirculate mainly through secondary lymphoid organs, including peripheral lymph nodes (PLNs). Here, we report that TCM, unlike naive T cells, can home to PLNs in both a CCR7-dependent and -independent manner. Homing experiments in paucity of lymph node T cells (plt/plt) mice, which do not express CCR7 ligands in secondary lymphoid organs, revealed that TCM migrate to PLNs at ∼20% of wild-type (WT) levels, whereas homing of naive T cells was reduced by 95%. Accordingly, a large fraction of endogenous CD8+ T cells in plt/plt PLNs displayed a TCM phenotype. Intravital microscopy of plt/plt subiliac lymph nodes showed that TCM rolled and firmly adhered (sticking) in high endothelial venules (HEVs), whereas naive T cells were incapable of sticking. Sticking of TCM in plt/plt HEVs was pertussis toxin sensitive and was blocked by anti-CXCL12 (SDF-1α). Anti-CXCL12 also reduced homing of TCM to PLNs in WT animals by 20%, indicating a nonredundant role for this chemokine in the presence of physiologic CCR7 agonists. Together, these data distinguish naive T cells from TCM, whereby only the latter display greater migratory flexibility by virtue of their increased responsiveness to both CCR7 ligands and CXCL12 during homing to PLN.
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DOI：
10.1084/jem.194.7.953
发表时间：
2001-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Weninger W;Crowley MA;Manjunath N;von Andrian UH
通讯作者：
von Andrian UH
影响因子：
56.9
作者：
Campbell, JJ;Hedrick, J;Butcher, EC
通讯作者：
Butcher, EC
影响因子：
64.5
作者：
Kaech, SM;Hemby, S;Ahmed, R
通讯作者：
Ahmed, R
影响因子：
15.9
作者：
Manjunath, N;Shankar, P;von Andrian, UH
通讯作者：
von Andrian, UH
DOI：
10.1073/pnas.97.23.12694
发表时间：
2000-11-07
影响因子：
11.1
作者：
Luther, SA;Tang, HL;Cyster, JG
通讯作者：
Cyster, JG