Dual role of anti-TNF therapy: Enhancement of TCR-mediated T cell activation in peripheral blood and inhibition of inflammation in target tissues
Dual role of anti-TNF therapy: Enhancement of TCR-mediated T cell activation in peripheral blood and inhibition of inflammation in target tissues
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DOI：
10.1016/j.clim.2011.01.015
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发表时间：
2011-05-01
影响因子：
8.6
通讯作者：
Reali, Eva
中科院分区：
文献类型：
--
作者：
Bose, Francesca;Raeli, Lorenzo;Reali, Eva
抗TNF治疗对患者全身免疫应答的影响尚未明确。在这里，我们研究了Th 1/Th 2/Th 17细胞因子的表达，活化和增殖的银屑病和炎症性肠病患者的外周血T细胞抗TNF治疗前和治疗期间。同时，我们计算了与临床反应的相关性，并监测了炎症组织活检中细胞因子的表达。我们证明了TNF阻断的双重作用。在外周血中，它增加了细胞因子如IL-17、IL-10和IFN-γ的表达，并增强了活化标志物的表达和CD 4 T细胞对TCR刺激的增殖反应。相比之下，在靶组织的活检中，TNF阻断减少了Th 17/Th 1细胞因子和早期炎症基因的表达。重要的是，对TCR刺激的增强的T细胞应答不会损害对治疗的临床应答，并且在应答患者中，伴随着靶组织中炎性基因的下调。(C)2011 Elsevier Inc. All rights reserved.
The impact of anti-TNF therapy on systemic immune responses in patients has not been clearly defined. Here, we examined Th1/Th2/Th17 cytokine expression, activation and proliferation of peripheral T cells from patients with psoriasis and inflammatory bowel disease before and during anti-TNF therapy. In parallel, we calculated the correlation with the clinical response and we monitored cytokine expression in biopsies from inflamed tissues. We evidenced a dual role of TNF-blockade. In peripheral blood, it increased the expression of cytokines such as IL-17, IL-10, and IFN-gamma, and enhanced the expression of activation markers and the proliferative response of CD4 T cells to TCR stimulation. By contrast, in biopsies from target tissues, TNF-blockade diminished the expression of Th17/Th1 cytokine and early inflammatory genes. Importantly, the enhanced T cell responses to TCR-stimulation did not impair the clinical response to the therapy and, in responder patients, occurred with the concomitant down-regulation of inflammatory genes in the target tissues. (C) 2011 Elsevier Inc. All rights reserved.