Pluschke G, Taube H, Krawinkel U, Pfeffer K, Wagner H, Classen M, Deusch K
II. Department of Internal Medicine, Technical University of Munich, Germany.
Immunobiology. 1994 Dec;192(1-2):77-93. doi: 10.1016/s0171-2985(11)80409-2.
Intraepithelial intestinal T lymphocytes (IEL) bearing alpha beta or gamma delta T cell receptors (TCR) are positioned to serve as a first line of defense against enteric pathogens. To investigate whether intestinal IEL are subject to antigenic selective forces distinct from that influencing (xp T cells in the peripheral blood (PBL), we performed a comparative analysis of V beta gene segment usage in IEL and PBL of immunologically normal donors by quantitative PCR. Primers for 22 different human TCR V beta gene segments of V beta gene segments families were used to analyze the repertoire of TCR beta chain transcripts in colonic IEL (c-IEL), in corresponding colonic lamina propria lymphocytes (c-LPL), and in peripheral blood lymphocytes. In each of the three individuals examined, a limited number (1-4 out of 22) of TCR V beta families predominated and accounted for more than 50% of the total beta chain transcripts from c-IEL, whereas in PBL and c-LPL a more even distribution of V beta gene families was observed. The dominating V beta gene families were V beta 2, V beta 3, V beta 6, V beta 8 and V beta 14. In one individual, V beta 3 comprised more than 40% of the entire repertoire of c-IEL beta chain transcripts. Sequence analysis of the predominant V beta 3 family in this individual revealed identical sequences in 13 of 17 clones analyzed. Human alpha beta TCR+ c-IEL could not be driven to proliferate or exhibit cytotoxic function in vitro however, PCR analysis for detection of lymphokine mRNA revealed constitutive production of several lymphokines known to exert trophic effects on intestinal epithelial cells and pro-inflammatory activities. Taken together, the striking degree of oligoclonality may indicate that the intraepithelial intestinal immune system is targeted to a limited set of hitherto unknown self- or foreign antigens present in the intestine and orchestrates intramucosal inflammatory and regenerative processes.
携带αβ或γδT细胞受体（TCR）的上皮内肠T淋巴细胞（IEL）可作为抵御肠道病原体的第一道防线。为了研究肠道IEL是否受到不同于影响外周血（PBL）中αβT细胞的抗原选择力的作用，我们通过定量PCR对免疫正常供体的IEL和PBL中的Vβ基因片段使用情况进行了比较分析。使用针对Vβ基因片段家族的22种不同人类TCR Vβ基因片段的引物，分析结肠IEL（c-IEL）、相应的结肠固有层淋巴细胞（c-LPL）和外周血淋巴细胞中TCRβ链转录本的库。在所检测的三个个体中，有限数量（22个中的1 - 4个）的TCR Vβ家族占主导地位，占c-IEL总β链转录本的50%以上，而在PBL和c-LPL中观察到Vβ基因家族的分布更为均匀。占主导地位的Vβ基因家族是Vβ2、Vβ3、Vβ6、Vβ8和Vβ14。在一个个体中，Vβ3占c-IELβ链转录本整个库的40%以上。对该个体中占主导地位的Vβ3家族进行序列分析，发现在所分析的17个克隆中有13个具有相同序列。然而，人αβTCR + c-IEL在体外不能被驱动增殖或表现出细胞毒性功能，用于检测淋巴因子mRNA的PCR分析显示，几种已知对肠道上皮细胞具有营养作用和促炎活性的淋巴因子有组成性产生。综上所述，显著的寡克隆程度可能表明上皮内肠道免疫系统针对肠道中存在的一组有限的迄今未知的自身或外来抗原，并协调黏膜内的炎症和再生过程。
