Cognate recognition of the endothelium induces HY-specific CD8+ T-lymphocyte transendothelial migration (diapedesis) in vivo
Cognate recognition of the endothelium induces HY-specific CD8+ T-lymphocyte transendothelial migration (diapedesis) in vivo
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DOI：
10.1182/blood-2003-08-2717
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发表时间：
2004-04-15
期刊：
影响因子：
20.3
通讯作者：
Lechler, RI
中科院分区：
文献类型：
--
作者：
Marelli-Berg, FM;James, MJ;Lechler, RI
内皮细胞（ECs）向运输T淋巴细胞呈递mhc肽复合物的生理意义尚不清楚。根据我们的观察，同源识别的ECs增强抗原特异性T淋巴细胞在体外的跨内皮迁移，我们提出，通过显示来自底层组织的抗原肽，ECs促进抗原特异性T细胞的募集。在这项研究中，我们使用体内T细胞募集模型，通过比较hy特异性T淋巴细胞进入抗原和非抗原组织的运输情况，验证了这一假设。在雄性小鼠腹膜间皮和血管中，H2分子内源性抗原的上调表达导致hy特异性T细胞的局部募集，而雌性小鼠则没有。活体显微镜实验分析了增生血管床中ec - hy特异性T细胞的相互作用，结果显示内皮的同源识别导致T细胞向组织的浸润增强，而不影响滚动和粘附。我们的结果与假设一致，即在炎症条件下，内皮的抗原呈递有助于T细胞介导的炎症的发展和特异性，有利于抗原特异性T细胞的选择性迁移。
The physiologic significance of MHC-peptide complex presentation by endothelial cells (ECs) to trafficking T lymphocytes remains unresolved. On the basis of our observation that cognate recognition of ECs enhanced transendothelial migration of antigen-specific T lymphocytes in vitro, we have proposed that by displaying antigenic peptides from the underlying tissue, ECs promote the recruitment of antigen-specific T cells. In this study, we have tested this hypothesis by comparing the trafficking of HY-specific T lymphocytes into antigenic and nonantigenic tissue using in vivo models of T-cell recruitment. Up-regulated expression of H2 molecules presenting endogenous antigen in the peritoneal mesothelium and vessels led to the local recruitment of HY-specific T cells in male, but not female, mice. Intravital microscopy experiments analyzing EC-HY-specific T-cell interactions in the cremasteric vascular bed revealed that cognate recognition of the endothelium results in enhanced diapedesis of T cells into the tissue, while not affecting rolling and adhesion. Our results are consistent with the hypothesis that, under inflammatory conditions, antigen presentation by the endothelium contributes to the development and specificity of T-cell-mediated inflammation by favoring the selective migration of antigen-specific T cells.