Chen Yaping, Chou Kevin, Fuchs Elaine, Havran Wendy L, Boismenu Richard
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14338-43. doi: 10.1073/pnas.212290499. Epub 2002 Oct 10.
gammadelta intraepithelial T lymphocytes (IEL) represent a major T cell population within the intestine of unclear functional relevance. The role of intestinal gammadelta IEL was evaluated in the dextran sodium sulfate (DSS) induced mouse colitis model system. Large numbers of gammadelta T cells, but not alphabeta T cells, were localized at sites of DSS-induced epithelial cell damage. gammadelta IEL in DSS treated mice expressed keratinocyte growth factor (KGF), a potent intestinal epithelial cell mitogen. gammadelta cell-deficient mice (TCRdelta(-/-)) and KGF-deficient mice (KGF(-/-)), but not alphabeta cell-deficient mice (TCRalpha(-/-)), were more prone than wild-type mice to DSS-induced mucosal injury and demonstrated delayed tissue repair after termination of DSS treatment. Termination of DSS treatment resulted in vigorous epithelial cell proliferation in wild-type mice but not in TCRdelta(-/-) mice or KGF(-/-) mice. These results suggest that gammadelta IEL help preserve the integrity of damaged epithelial surfaces by providing the localized delivery of an epithelial cell growth factor.
γδ上皮内T淋巴细胞(IEL)是肠道内主要的T细胞群体,其功能相关性尚不清楚。在葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎模型系统中评估了肠道γδ IEL的作用。大量的γδ T细胞而非αβ T细胞定位于DSS诱导的上皮细胞损伤部位。DSS处理小鼠中的γδ IEL表达角质形成细胞生长因子(KGF),这是一种有效的肠上皮细胞促有丝分裂原。γδ细胞缺陷小鼠(TCRδ(-/-))和KGF缺陷小鼠(KGF(-/-)),而非αβ细胞缺陷小鼠(TCRα(-/-)),比野生型小鼠更易发生DSS诱导的黏膜损伤,并且在DSS处理终止后显示出组织修复延迟。DSS处理的终止导致野生型小鼠中上皮细胞剧烈增殖,但在TCRδ(-/-)小鼠或KGF(-/-)小鼠中则不然。这些结果表明,γδ IEL通过提供上皮细胞生长因子的局部递送,有助于维持受损上皮表面的完整性。