Lefrançois L, Parker C M, Olson S, Muller W, Wagner N, Schön M P, Puddington L
Division of Rheumatic Diseases, University of Connecticut Health Center, Farmington, Connecticut 06037, USA.
J Exp Med. 1999 May 17;189(10):1631-8. doi: 10.1084/jem.189.10.1631.
The requirement of beta7 integrins for lymphocyte migration was examined during an ongoing immune response in vivo. Transgenic mice (OT-I) expressing an ovalbumin-specific major histocompatibility complex class I-restricted T cell receptor for antigen were rendered deficient in expression of all beta7 integrins or only the alphaEbeta7 integrin. To quantitate the relative use of beta7 integrins in migration in vivo, equal numbers of OT-I and OT-I-beta7(-/-) or OT-I-alphaE-/- lymph node (LN) cells were adoptively transferred to normal mice. Although OT-I-beta7(-/-) LN cells migrated to mesenteric LN and peripheral LN as well as wild-type cells, beta7 integrins were required for naive CD8 T cell and B cell migration to Peyer's patch. After infection with a recombinant virus (vesicular stomatitis virus) encoding ovalbumin, beta7 integrins became critical for migration of activated CD8 T cells to the mesenteric LN and Peyer's patch. Naive CD8 T cells did not enter the lamina propria or the intestinal epithelium, and the majority of migration of activated CD8 T cells to the small and large intestinal mucosa, including the epithelium, was beta7 integrin-mediated. The alphaEbeta7 integrin appeared to play no role in migration during a primary CD8 T cell immune response in vivo. Furthermore, despite dramatic upregulation of alphaEbeta7 by CD8 T cells after entry into the epithelium, long-term retention of intestinal intraepithelial lymphocytes was also alphaEbeta7 independent.
在体内正在进行的免疫反应过程中，研究了β7整合素对淋巴细胞迁移的需求。表达针对抗原的卵清蛋白特异性主要组织相容性复合体I类限制性T细胞受体的转基因小鼠（OT-I），使其所有β7整合素或仅αEβ7整合素的表达缺失。为了定量β7整合素在体内迁移中的相对使用情况，将等量的OT-I和OT-I-β7（-/-）或OT-I-αE-/-淋巴结（LN）细胞过继转移到正常小鼠体内。尽管OT-I-β7（-/-）LN细胞迁移到肠系膜淋巴结和外周淋巴结的情况与野生型细胞一样，但天然CD8 T细胞和B细胞迁移到派尔集合淋巴结需要β7整合素。在用编码卵清蛋白的重组病毒（水疱性口炎病毒）感染后，β7整合素对于活化的CD8 T细胞迁移到肠系膜淋巴结和派尔集合淋巴结变得至关重要。天然CD8 T细胞不进入固有层或肠上皮，并且活化的CD8 T细胞向小肠和大肠黏膜（包括上皮）的大多数迁移是由β7整合素介导的。在体内原发性CD8 T细胞免疫反应过程中，αEβ7整合素似乎在迁移中不起作用。此外，尽管CD8 T细胞进入上皮后αEβ7会显著上调，但肠道上皮内淋巴细胞的长期留存也不依赖αEβ7。
