ANALYSIS OF THE PERIPHERAL-BLOOD T-CELL RECEPTOR (TCR) REPERTOIRE IN MONOZYGOTIC TWINS DISCORDANT FOR CROHNS-DISEASE
ANALYSIS OF THE PERIPHERAL-BLOOD T-CELL RECEPTOR (TCR) REPERTOIRE IN MONOZYGOTIC TWINS DISCORDANT FOR CROHNS-DISEASE
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DOI：
10.3109/08916939409010660
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发表时间：
1994-01-01
期刊：
影响因子：
3.5
通讯作者：
SILVER, J
中科院分区：
文献类型：
--
作者：
GULWANIAKOLKAR, B;SHALON, L;SILVER, J
T细胞参与克罗恩病（CD）的炎性过程通过活化的T细胞及其细胞因子在活动性发炎的CD组织中的增加而明显。基于与正常对照相比，显著比例的CD患者在其外周血中表达升高水平的V β 8 + T细胞的观察，已经表明CD可能涉及超抗原。为了确定超抗原是否可能在CD的发病机制中发挥作用，我们比较了四对CD不一致的单卵双胞胎的TCR库。通过使用单卵双胞胎，我们可以排除HLA和其他基因对TCR库的影响。通过使用一组V片段特异性mAb和使用V β特异性寡核苷酸引物的定量聚合酶链反应（qPCR）分析TCR库。在所有情况下，受影响和未受影响的同胞的TCR库是惊人的相似。与同卵双生子相比，我们没有观察到任何TCR片段在所有受影响的同胞中在频率或表达水平上一致改变。此外，我们没有看到CD同胞外周血中V β 8 + T细胞相对于其正常对应物的增加。这些研究表明，CD的存在不会以任何明显的方式改变外周血的TCR库，并反对超抗原在CD病因学或发病机制中的作用。
T cell involvement in the inflammatory process of Crohn's Disease (CD) is evident by an increase in activated T cells and their cytokines in actively inflamed CD tissue. It has been suggested that CD may involve a superantigen based on the observation that a significant proportion of CD patients express elevated levels of Vbeta8+ T cells in their peripheral blood compared to normal controls. In order to determine whether a superantigen might play a role in the pathogenesis of CD we have compared the TCR repertoires of four pairs of monozygotic twins discordant for CD. By using monozygotic twins, we could rule out the effects of HLA and other genes on the TCR repertoire. The TCR repertoires were analyzed by using a panel of V-segment-specific mAb and by quantitative polymerase chain reaction (qPCR) using Vbeta-specific oligonucleotide primers. In all cases the TCR repertoires of the affected and unaffected sibs were strikingly similar. We did not observe any TCR segment that was consistently altered in frequency or expression levels in all of the affected sibs compared to their identical twin. Furthermore, we did not see an increase in Vbeta8+ T cells in the peripheral blood of the CD sibs relative to their normal counterpart. These studies suggest that the presence of CD does not alter the TCR repertoire of peripheral blood in any obvious way and argue against the role of a superantigen in the etiology or pathogenesis of CD.