Polyfunctional CD4+ T-Cell Induction in Neutralizing Antibody-Triggered Control of Simian Immunodeficiency Virus Infection
Polyfunctional CD4+ T-Cell Induction in Neutralizing Antibody-Triggered Control of Simian Immunodeficiency Virus Infection
复制标题
多功能 CD4 T 细胞诱导中和抗体触发的猴免疫缺陷病毒感染控制
作者：
Takuya Yamamoto;N. Iwamoto;Hiroyuki Yamamoto;T. Tsukamoto;T. Kuwano;A. Takeda;M. Kawada;Y. Tsunetsugu;T. Matano
人类免疫缺陷病毒（HIV）和猿猴免疫缺陷病毒（SIV）感染的特征是记忆性CD 4 + T细胞的快速耗竭和中和抗体（NAb）应答的延迟诱导。虽然有人推测，感染后NAb诱导可能只有一个有限的抑制作用的主要艾滋病毒复制，最近的一项研究表明，一个单一的被动NAb免疫恒河猴1周后，SIV的挑战，可以导致在设定点的病毒载量减少，表明感染后NAb反应病毒控制的可能贡献。然而，解释这种NAb触发的SIV控制的机制仍不清楚。在这里，我们报告快速诱导病毒特异性多功能T细胞反应后，被动NAb免疫感染后。对γ干扰素、肿瘤坏死因子α、白细胞介素-2、巨噬细胞炎性蛋白1β和CD 107 a的SIV GAG特异性应答的分析显示，由这些应答的多重性定义的GAG特异性CD 4 + T细胞的多功能性在NAb免疫的动物的急性期显著升高。在慢性期，尽管没有可检测的NAb，病毒控制得以维持，伴随着多功能的GAG特异性T细胞应答。这些结果暗示了NAb触发的病毒控制中的病毒特异性多功能CD 4 + T细胞应答，表明NAb和T细胞之间可能存在协同作用以控制HIV/SIV复制。
ABSTRACT Rapid depletion of memory CD4+ T cells and delayed induction of neutralizing antibody (NAb) responses are characteristics of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections. Although it was speculated that postinfection NAb induction could have only a limited suppressive effect on primary HIV replication, a recent study has shown that a single passive NAb immunization of rhesus macaques 1 week after SIV challenge can result in reduction of viral loads at the set point, indicating a possible contribution of postinfection NAb responses to virus control. However, the mechanism accounting for this NAb-triggered SIV control has remained unclear. Here, we report rapid induction of virus-specific polyfunctional T-cell responses after the passive NAb immunization postinfection. Analysis of SIV Gag-specific responses of gamma interferon, tumor necrosis factor alpha, interleukin-2, macrophage inflammatory protein 1β, and CD107a revealed that the polyfunctionality of Gag-specific CD4+ T cells, as defined by the multiplicity of these responses, was markedly elevated in the acute phase in NAb-immunized animals. In the chronic phase, despite the absence of detectable NAbs, virus control was maintained, accompanied by polyfunctional Gag-specific T-cell responses. These results implicate virus-specific polyfunctional CD4+ T-cell responses in this NAb-triggered virus control, suggesting possible synergism between NAbs and T cells for control of HIV/SIV replication.
影响因子：
20.3
作者：
Betts, Michael R.;Nason, Martha C.;Koup, Richard A.
通讯作者：
Koup, Richard A.
影响因子：
56.9
作者：
Rosenberg, ES;Billingsley, JM;Walker, BD
通讯作者：
Walker, BD
影响因子：
56.9
作者：
Schmitz, JE;Kuroda, MJ;Reimann, KA
通讯作者：
Reimann, KA