CD4+IL-21+T cells are correlated with regulatory T cells and IL-21 promotes regulatory T cells survival during HIV infection
CD4+IL-21+T cells are correlated with regulatory T cells and IL-21 promotes regulatory T cells survival during HIV infection
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CD4( )IL-21( )T 细胞与调节性 T 细胞相关，IL-21 在 HIV 感染期间促进调节性 T 细胞存活
DOI：
10.1016/j.cyto.2016.12.012
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发表时间：
2017-03-01
期刊：
影响因子：
3.8
通讯作者：
Shang, Hong
中科院分区：
文献类型：
--
作者：
Zhang, Zi-Ning;Bai, Li-Xin;Shang, Hong
前言：在人类免疫缺陷病毒(HIV)感染过程中，IL-21在不促进T细胞活化的情况下，增强T细胞和自然杀伤细胞的存活和抗病毒功能，使其成为抗HIV免疫治疗的良好佐剂。由于细胞因子的多效性和冗余性，全面了解IL-21在免疫反应调节中的作用是至关重要的。调节性T细胞(Tregs)在免疫调节中发挥重要作用，在某些情况下是免疫治疗效果的决定因素。本研究探讨了在HIV感染过程中IL-21对Tregs的直接作用。方法：研究34例HIV治疗初治患者外周血中CD4(+)IL21(+)T细胞与Tregs的关系。观察IL-21对HIV感染者外周血中CD4(+)、CD25(+)、CD127(低)Tregs细胞凋亡、增殖及CTLA-4、TGF-β表达的影响，并与其他常见的伽玛链细胞因子作用进行比较。结果：发现CD4(+)、CD25(+)、CD127(低)Tregs的频率和绝对数与CD4(+)、CD25(+)、CD127(低)Tregs的频率或绝对数呈正相关。与单纯介质对照组相比，IL-21、IL-7、IL-15能显著减少Tregs的凋亡率(p<；0.05)。IL-21对Tregs的增殖无明显促进作用，而IL-2、IL-7和IL-15可显著促进Tregs的增殖(p<；0.05)。IL-21可促进HIV感染者Tregs分泌CTLA-4(p<；0.05)，但不能诱导Tregs分泌转化生长因子-β。经IL-21治疗后，HIV感染者和正常对照Tregs诱导的细胞凋亡、增殖以及CTLA-4和TGF-β的表达均无显著差异。体外实验表明，IL-21可显著增强Tregs对CD8(+)T细胞的干扰素-γ表达的抑制作用。结论：IL-21可促进Tregs的存活和CTLA-4的表达，增强Tregs在HIV感染过程中的抑制能力。这些结果拓宽了对HIV发病机制的理解，并为HIV干预提供了关键信息。(C)2016爱思唯尔有限公司。保留所有权利。
Introduction: IL-21 enhances T and natural killer cells survival and antiviral functions without promoting T cell activation during HIV infection, which makes it a better adjuvant in anti-HIV immunotherapy. Due to the pleiotropy and redundancy of cytokines, it is vital to have a comprehensive knowledge of the role of IL-21 in the regulation of immune responses. Regulatory T cells (Tregs) play an important role in immune regulation and are a determinant of immune therapeutic efficacy in certain circumstances. In this study, we explored the direct effect of IL-21 on Tregs during HIV infection, which has not been addressed before.Methods: Thirty-four HIV treatment-naive patients were enrolled and the relationship between CD4(+)IL21(+)T cells and Tregs were studied. The effects of IL-21 on CD4(+)CD25(+)CD127(low) Tregs' apoptosis, proliferation, and CTLA-4 and TGF-beta expression in HIV-infected patients was investigated and compared with the effect of other common gamma-chain cytokines.Results: We found the percentage and absolute numbers of CD4(+)IL-21(+)T cells were positively related to the frequency or absolute numbers of CD4(+)CD25(+) or CD4(+)CD25(+)CD127(low) Tregs. Compared with the media-alone control, IL-21, IL-7, and IL-15 could significantly reduce apoptosis of Tregs (p < 0.05). IL 21 did not promote the proliferation of Tregs as compared with media alone, while IL-2, IL-7, and IL 15 could significantly increase the proliferation of Tregs (p < 0.05). IL-21 enhanced CTLA-4 expression by Tregs (p < 0.05), but could not induce TGF-beta secretion of Tregs from HIV infected patients. There were no significant differences of the fold induction of apoptosis, proliferation, or CTLA-4 and TGF-beta expression by Tregs from HIV-infected patients and normal controls after IL-21 treatment. In vitro experiment showed that pretreatment with IL-21 significantly enhanced the suppressive effect of Tregs on CD8(+) T cells' IFN-gamma expression.Conclusion: We conclude that IL-21 promotes the survival and CTLA-4 expression of Tregs and enhanced the suppressive capacity of Tregs during HIV infection. These results broaden the understanding of HIV pathogenesis and provide critical information for HIV interventions. (C)2016 Elsevier Ltd. All rights reserved.