Ishikawa H, Li Y, Abeliovich A, Yamamoto S, Kaufmann S H, Tonegawa S
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139.
Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8204-8. doi: 10.1073/pnas.90.17.8204.
We have analyzed the cytolytic activity of freshly isolated intraepithelial T cells (i-IEL) from the intestines of several different mouse strains in an anti-T-cell receptor monoclonal antibody-mediated redirected lysis assay. The cytolytic activity of gamma delta i-IEL but not that of alpha beta i-IEL was strain dependent. Mouse strains could be divided into high (H), marginal (M), and null (N) strains. The anti-gamma delta T-cell receptor monoclonal antibody-induced interferon gamma production showed the same strain-dependent variability, but the proliferative responses to gamma delta T-cell receptor crosslinking did not show this variability. The N phenotype of gamma delta i-IEL was found to be dominant in (H x N)F1 mice. In radiation bone-marrow chimeras the H/N phenotype was determined by the genotype of the reconstituting bone-marrow-derived cells but was not determined by the genotype of the radioresistant host cells. Analysis of (H x N)F1 backcross animals indicated that at least two genes are involved in determination of the H/N phenotype. One of these genes is major-histocompatibility-complex linked. No difference in the use of the variable region segment of the gamma-chain or delta-chain was seen between the gamma delta i-IEL from H and N strains. Various models that might explain the strain-dependent gamma delta i-IEL phenotypes are discussed.
我们在抗T细胞受体单克隆抗体介导的重定向裂解试验中,分析了从几种不同小鼠品系的肠道中新鲜分离的上皮内T细胞(i-IEL)的细胞溶解活性。γδ i-IEL的细胞溶解活性具有品系依赖性,而αβ i-IEL则不然。小鼠品系可分为高(H)、边缘(M)和无(N)品系。抗γδ T细胞受体单克隆抗体诱导的干扰素γ产生表现出相同的品系依赖性变异性,但对γδ T细胞受体交联的增殖反应未表现出这种变异性。发现γδ i-IEL的N表型在(H×N)F1小鼠中占主导地位。在辐射骨髓嵌合体中,H/N表型由重建的骨髓来源细胞的基因型决定,而不由抗辐射宿主细胞的基因型决定。对(H×N)F1回交动物的分析表明,至少有两个基因参与H/N表型的决定。其中一个基因与主要组织相容性复合体连锁。在H品系和N品系的γδ i-IEL之间,未观察到γ链或δ链可变区片段使用上的差异。本文讨论了可能解释品系依赖性γδ i-IEL表型的各种模型。