Rust C, Kooy Y, Peña S, Mearin M L, Kluin P, Koning F
Department of Immunohematology and Bloodbank, Academic Hospital, Leiden, The Netherlands.
Scand J Immunol. 1992 Apr;35(4):459-68. doi: 10.1111/j.1365-3083.1992.tb02881.x.
Increased numbers of TcR gamma delta + T cells are present in the small intestinal epithelium of patients with coeliac disease (CoD). Their function, however, is unknown. In order to facilitate detailed functional studies, intestinal gamma delta T cells have been isolated from small intestinal biopsies of patients with CoD (n = 18) and controls (n = 14). As expected, increased numbers of V delta 1+ TcR gamma delta + T cells were detected in freshly isolated intraepithelial cell suspensions (IEL) from CoD patients. Also, in the in vitro expanded IEL T-cell populations from CoD patients the numbers of V delta 1+ TcR gamma delta + T cells were increased compared with similar cell cultures from control patients. From IEL cultures derived from six CoD patients, 107 T-cell clones were generated by limiting dilution and analysed. Sixty of these clones were either CD4 or CD8 positive TcR alpha beta + clones. The remaining 47 clones expressed the TcR gamma delta. Further phenotypical analysis of the gamma delta T-cell clones indicated that the TcR gamma delta + T-cell population in the small intestinal epithelium of CoD patients is heterogeneous: four TcR gamma delta phenotypes could be detected and, although the majority of the TcR gamma delta + T cells were CD4 CD8, gamma delta T-cell clones expressing either a CD8 alpha alpha homodimer, a CD8 alpha beta heterodimer or CD4 were also identified. In contrast to the TCR alpha beta + IEL, most TcR gamma delta + IEL were CD5 negative. Furthermore, biochemical analysis indicated that the increase in V delta 1+ gamma delta T cells in the small intestinal epithelium of CoD patients was not the result of a monoclonal expansion. The small intestinal epithelium-derived gamma delta T-cell clones were functional in vitro since the majority of these clones were able to lyse target cell lines such as K562. Molt4 and Daudi. These novel findings therefore indicate that the gamma delta T cells in the small intestine of CoD patients represent a heterogeneous population and that such cells are functional in vitro. The isolation and the in vitro propagation and cloning of these cells may open new avenues for the study of the putative immune mechanisms leading to coeliac disease.
乳糜泻（CoD）患者的小肠上皮中存在数量增多的TcRγδ + T细胞。然而，它们的功能尚不清楚。为了便于进行详细的功能研究，已从CoD患者（n = 18）和对照者（n = 14）的小肠活检组织中分离出肠道γδ T细胞。正如预期的那样，在从CoD患者新鲜分离的上皮内细胞悬液（IEL）中检测到Vδ1 + TcRγδ + T细胞数量增加。此外，与对照患者的类似细胞培养物相比，CoD患者体外扩增的IEL T细胞群体中Vδ1 + TcRγδ + T细胞的数量也增加。从6名CoD患者的IEL培养物中，通过有限稀释产生了107个T细胞克隆并进行了分析。其中60个克隆是CD4或CD8阳性的TcRαβ +克隆。其余47个克隆表达TcRγδ。对γδ T细胞克隆的进一步表型分析表明，CoD患者小肠上皮中的TcRγδ + T细胞群体是异质性的：可以检测到四种TcRγδ表型，尽管大多数TcRγδ + T细胞是CD4 CD8，但也鉴定出表达CD8αα同二聚体、CD8αβ异二聚体或CD4的γδ T细胞克隆。与TCRαβ + IEL相反，大多数TcRγδ + IEL是CD5阴性的。此外，生化分析表明，CoD患者小肠上皮中Vδ1 + γδ T细胞的增加不是单克隆扩增的结果。从小肠上皮衍生的γδ T细胞克隆在体外具有功能，因为这些克隆中的大多数能够裂解靶细胞系，如K562、Molt4和Daudi。因此，这些新发现表明，CoD患者小肠中的γδ T细胞代表一个异质性群体，并且这些细胞在体外具有功能。这些细胞的分离、体外增殖和克隆可能为研究导致乳糜泻的假定免疫机制开辟新途径。
