Changes in the peripheral blood T-cell receptor V beta repertoire in vivo and in vitro during shigellosis
Changes in the peripheral blood T-cell receptor V beta repertoire in vivo and in vitro during shigellosis
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DOI：
10.1128/iai.64.4.1391-1399.1996
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发表时间：
1996-04-01
影响因子：
3.1
通讯作者：
Christensson, B
中科院分区：
文献类型：
--
作者：
Islam, D;Wretlind, B;Christensson, B
已经观察到志贺氏菌病期间外周血中T细胞的顺序活化（D. Islam，P. K，Bardhan，A. A. Lindberg和B。克里斯滕森，感染，免疫。63：2941-2949，1995）。为了进一步研究志贺氏菌感染过程中的细胞应答，分析了外周血中T细胞受体（TCR）库的变化。用于监测志贺氏菌病期间患者血液中T细胞亚群的TCR V β库变化的假设是志贺氏菌抗原可以调节携带能够识别志贺氏菌特异性表位或超抗原的TCR的T细胞的功能。这种对表达某些TCR V β类型的T细胞的选择性偏好可能导致这些T细胞的扩增或缺失。其中志贺菌1型14例，福氏志贺菌13例，外周血CD 4（+）和CD 8（+）T细胞亚群的TCRV β库的变化已经用一组9种抗Vp单克隆抗体通过流式细胞术进行了分析，20名来自孟加拉国的健康男性和20名来自瑞典的健康男性作为对照，与孟加拉国对照相比，患者具有表达V β 2、V β 3和V β 17的CD 4（+）T细胞的频率增加，在疾病发作后第7天达到最大值，表达V β 5.1的CD 4（+）T细胞的频率仅在S.志贺氏菌感染患者的外周血T细胞也以TCR V β特异性方式对体外刺激产生应答。大肠杆菌1和滋贺毒素增强了表达V β 2、V β 3、V β 5.1、V β 13.6和V β 17的细胞的频率，尤其是在第7天获得的样品中。在体内和体外发现的V β 17可能表明在志贺氏菌病中抗原或超抗原被呈递给免疫系统并优先激活T细胞亚群中的某些TCR V β类型，志贺氏菌病期间血液中TCR V β库变化的动力学可能表明，在局部活化后，抗原活化的T细胞可以在血液中回收并在体外再刺激。如果通过TCR序列分析对肠道和血液中的T细胞进行平行分析来证实，我们的研究结果提示的可能性将有助于进一步分析细胞介导的免疫应答在志贺氏菌感染的发病机制和保护中的作用。
A sequential activation of T cells in peripheral blood during shigellosis has been observed (D. Islam, P. K, Bardhan, A. A. Lindberg, and B. Christensson, Infect, Immun. 63:2941-2949, 1995), To further investigate the cellular response during the course of Shigella infection, changes in the T-cell receptor (TCR) repertoire in the peripheral blood were analyzed, The hypothesis for monitoring changes in the TCR V beta repertoire of T-cell subsets in blood in patients during shigellosis was that Shigella antigens may modulate the function of T cells carrying TCRs capable of recognizing Shigella-specific epitopes or superantigens. Such a selective preference for T cells expressing certain TCR V beta types could lead to the expansion or deletion of these T cells, In the present study of 27 adult male Bangladeshi patients with dysentery (14 cases caused by Shigella dysenteriae 1 and 13 cases caused by Shigella flexneri), the changes in the TCR V beta repertoire of peripheral blood CD4(+) and CD8(+) T-cell subsets have been analyzed with a panel of nine anti-Vp monoclonal antibodies by how cytometry, Twenty healthy males from Bangladesh and 20 healthy males from Sweden served as controls, Compared with the Bangladeshi controls, the patients had an increased frequency of CD4(+) T cells expressing V beta 2, V beta 3, and V beta 17, with a maximum at day 7 after the onset of disease, The frequency of CD4(+) T cells expressing V beta 5.1 was increased only in patients with S. flexneri infection, Peripheral blood T cells from Shigella-infected patients also responded to in vitro stimulation in a TCR V beta-specific manner, Stimulation with heat-killed S. dysenteriae 1 and Shiga toxin enhanced the frequency of cells expressing V beta 2, V beta 3, V beta 5.1, V beta 13.6, and V beta 17, especially in samples obtained at day 7, The enhanced frequency of cells expressing V beta 2, V beta 3, V beta 5.1, and V beta 17 found both in in vivo and in vitro could suggest that in shigellosis antigens or superantigens are presented to the immune system and preferentially activate certain TCR V beta types in T-cell subsets, The kinetics of the change in the TCR V beta repertoire in blood during shigellosis may indicate that following local activation, the antigen activated T cells can be retrieved in the blood and restimulated in vitro, If confirmed by parallel analysis of T cells in the gut and blood by TCR sequence analysis, the possibility suggested by our findings would facilitate further analysis of the role of cell-mediated immune responses in the pathogenesis of and protection against Shigella infection.