Antigen stimulation induces HIV envelope gp120-specific CD4+ T cells to secrete CCR5 ligands and suppress HIV infection
Antigen stimulation induces HIV envelope gp120-specific CD4+ T cells to secrete CCR5 ligands and suppress HIV infection
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DOI：
10.1016/j.virol.2007.07.031
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发表时间：
2007-12-05
期刊：
影响因子：
3.7
通讯作者：
Hioe, Catarina E.
中科院分区：
文献类型：
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作者：
Kaur, Gurvinder;Tuen, Michael;Hioe, Catarina E.
CD 4（+）T细胞对于有效对抗HIV的免疫反应至关重要，但它们也是病毒靶向的主要细胞类型。为了研究保护这些细胞免受感染的关键因素，我们评估了HIV gp 120特异性人CD 4（+）T细胞产生抑制HIV的趋化因子的能力，并确定了它们在抑制细胞感染中的作用。CD 4（+）T细胞的抗原刺激引起大量CCR 5趋化因子MIP-1 α（CCL 3）、MIP-1 β（CCL 4）和RANTES（CCL 5）的产生。这些CCR 5配体的产生比IFN-γ或IL-2的产生更容易且可重复地检测。重要的是，与CCR 5配体的分泌相关，抗原刺激使这些CD 4（+）T细胞对CCR 5-tropic HIV-1更具抗性。相反，在没有抗原刺激的情况下，细胞很容易被病毒感染，感染后，它们产生MIP-1 β和IFN-γ的能力迅速下降。因此，触发HIV特异性CD 4（+）T细胞以引发抗病毒趋化因子的稳健和快速产生的疫苗将是有利的。这种反应将保护病毒特异性CD 4（+）T细胞免受HIV感染，并保留其在建立和维持针对病毒的持久免疫力方面的关键功能。(C)2007年爱思唯尔公司All rights reserved.
CD4(+) T cells are critical for effective immune responses against HIV, but they are also the main cell type targeted by the virus. To investigate the key factors that could protect these cells from infection, we evaluated the capacity of HIV gp120-specific human CD4(+) T cells to produce chemokines that inhibit HIV and determined their contribution in suppressing infection in the cells. Antigen stimulation of the CD4(+) T cells elicited production of high amounts of CCR5 chemokines MIP-1 alpha (CCL3), MIP-1 beta (CCL4), and RANTES (CCL5). Production of these CCR5 ligands was more readily and reproducibly detected than that of IFN-gamma or IL-2. Importantly, in association with secretion of the CCR5 ligands, antigen stimulation made these CD4(+) T cells more resistant to CCR5-tropic HIV-1. Conversely, in the absence of antigen stimulation, the cells were readily infected by the virus, and after infection, their capacity to produce MIP-1 beta and IFN-gamma rapidly declined. Thus, vaccines that trigger HIV-specific CD4(+) T cells to elicit robust and rapid production of anti-viral chemokines would be advantageous. Such responses would protect virus-specific CD4(+) T cells from HIV infection and preserve their critical functions in mounting and maintaining long-lasting immunity against the virus. (C) 2007 Elsevier Inc. All rights reserved.