Regulatory and Helper Follicular T Cells and Antibody Avidity to Simian Immunodeficiency Virus Glycoprotein 120.
Regulatory and Helper Follicular T Cells and Antibody Avidity to Simian Immunodeficiency Virus Glycoprotein 120.
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DOI：
10.4049/jimmunol.1402699
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发表时间：
2015-10-01
期刊：
影响因子：
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通讯作者：
Vaccari M
中科院分区：
文献类型：
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作者：
Blackburn MJ;Zhong-Min M;Caccuri F;McKinnon K;Schifanella L;Guan Y;Gorini G;Venzon D;Fenizia C;Binello N;Gordon SN;Miller CJ;Franchini G;Vaccari M
滤泡调节性T细胞（TFR）是一种抑制性CD 4 + T细胞亚群，在抗原呈递过程中通过上调趋化因子受体CXCR 5迁移到生发中心（GC）。在GC中，TFR控制T滤泡辅助细胞（TFH）的扩增并调节高亲和力抗原特异性反应的发展。我们在健康恒河猴的淋巴组织中鉴定并表征了TFR为CXCR 5 + CCR 7 −-“滤泡”T调节细胞（Treg），并在明确的HIV发病机制动物模型中研究了它们在整个感染过程中的动态。TFR被SIVmac 251感染，并且具有与CXCR 5 − CCR 7 +-“T区”TREG和TFH相当的SIV-DNA水平。与SIV相关的TFH在慢性感染期的扩增相反，我们观察到细胞悬液中TFR频率明显降低，以及完整淋巴结GC中CD 3 + Foxp 3+细胞减少。TFR频率与TFH的百分比呈负相关，有趣的是，与识别SIV-gp 120包膜蛋白的抗体的亲合力呈负相关。我们的研究结果表明，在慢性感染过程中的TFH/TFR的比例变化，并提出了可能的机制TFH细胞在HIV/SIV感染的不受限制的扩张。
T follicular regulatory cells (TFR) are a suppressive CD4+ T cell subset that migrates to germinal centers (GC) during antigen presentation by up-regulating the chemokine receptor CXCR5. In the GC, TFR control T follicular helper cells (TFH) expansion and modulate the development of high-affinity antigen specific responses. Here we identified and characterized TFR as CXCR5+ CCR7−-“follicular” T regulatory cells (TREG) in lymphoid tissues of healthy rhesus macaques, and we studied their dynamic throughout infection in a well-defined animal model of HIV pathogenesis. TFR were infected by SIVmac251 and had comparable levels of SIV-DNA to CXCR5− CCR7+-“T-zone” TREG and TFH. Contrary to the SIV-associated TFH expansion in the chronic phase of infection, we observed an apparent reduction of TFR frequency in cell suspension, as well as a decrease of CD3+ Foxp3+ cells in the GC of intact lymph nodes. TFR frequency was inversely associated with the percentage of TFH and, interestingly, with the avidity of the antibodies that recognize the SIV-gp120 envelope protein. Our findings show changes in the TFH/TFR ratio during chronic infection and suggest possible mechanisms for the unchecked expansion of TFH cells in HIV/SIV infection.