Presentation of antigen by endothelial cells and chemoattraction are required for homing of insulin-specific CD8+ T cells.
Presentation of antigen by endothelial cells and chemoattraction are required for homing of insulin-specific CD8+ T cells.
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DOI：
10.1084/jem.20021378
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发表时间：
2003-03-03
期刊：
影响因子：
--
通讯作者：
Chervonsky AV
中科院分区：
文献类型：
--
作者：
Savinov AY;Wong FS;Stonebraker AC;Chervonsky AV
激活的胰岛素特异性 CD8+ T 细胞（IS-CD8+ 细胞）归巢于胰腺，破坏 β 细胞，并在转移到易患糖尿病的 NOD 小鼠体内后迅速引起糖尿病。令人惊讶的是，它们还会导致先前没有炎症的小鼠品系患糖尿病。因此，我们假设胰岛特异性归巢可能部分依赖于 IS-CD8+ 细胞对胰腺内皮细胞呈现的同源主要组织相容性复合物 (MHC)/肽复合物的识别，胰腺内皮细胞从 β 细胞获取抗原（胰岛素）。事实上，在缺乏 MHC I 类表达或特定肽呈递或胰岛素分泌受损的小鼠中，胰岛特异性归巢被废除。此外，我们发现 IS-CD8+ 细胞直接识别胰岛器官培养物中的胰腺内皮细胞。 IS-CD8+ 细胞 T 细胞受体 (TCR) 的触发导致这些细胞表达的整合素被激活。此外，趋化因子，特别是 SLC (CCL21)，也是 IS-CD8+ 细胞粘附至内皮单层和体内成功归巢所必需的。因此，通过 TCR 和趋化因子受体的信号传导协同作用，确保 T 细胞与胰腺内皮牢固粘附。因此，内皮细胞的抗原交叉呈递能力可能有助于活化的T淋巴细胞特异性归巢至由其他细胞类型产生抗原的组织。
Activated insulin-specific CD8+ T cells (IS-CD8+ cells) home to the pancreas, destroy β cells, and cause rapid diabetes upon transfer into diabetes-prone NOD mice. Surprisingly, they also cause diabetes in mouse strains that are free of preexistent inflammation. Thus, we hypothesized that islet-specific homing may be in part dependent on IS-CD8+ cells' recognition of the cognate major histocompatibility complex (MHC)/peptide complexes presented by pancreatic endothelial cells, which acquire the antigen (insulin) from β cells. In fact, islet-specific homing was abrogated in mice that lack MHC class I expression, or presentation of the specific peptide, or have impaired insulin secretion. Moreover, we found that IS-CD8+ cells directly recognized pancreatic endothelial cells in islet organ cultures. Triggering of IS-CD8+ cells' T cell receptor (TCR) led to activation of integrins expressed by these cells. In addition, chemokines, particularly SLC (CCL21), were also required for IS-CD8+ cells' adhesion to endothelial monolayers and for successful homing in vivo. Thus, signaling through TCR and chemokine receptors work in concert to assure firm adhesion of T cells to the pancreatic endothelium. The antigen cross-presentation ability of endothelia may therefore contribute to the specificity of homing of activated T lymphocytes to the tissues where antigens are generated by other cell types.
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影响因子：
56.9
作者：
Campbell, JJ;Hedrick, J;Butcher, EC
通讯作者：
Butcher, EC
DOI：
10.1084/jem.191.11.1957
发表时间：
2000-06-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Castellino F;Boucher PE;Eichelberg K;Mayhew M;Rothman JE;Houghton AN;Germain RN
通讯作者：
Germain RN
影响因子：
15.9
作者：
BARON, JL;REICH, EP;JANEWAY, CA
通讯作者：
JANEWAY, CA
影响因子：
15.9
作者：
Kayo, T;Koizumi, A
通讯作者：
Koizumi, A
影响因子：
15.9
作者：
HANNINEN, A;TAYLOR, C;MICHIE, SA
通讯作者：
MICHIE, SA