IL-10 directly suppresses CD4 but not CD8 T cell effector and memory responses following acute viral infection
IL-10 directly suppresses CD4 but not CD8 T cell effector and memory responses following acute viral infection
复制标题
DOI：
10.1073/pnas.0914500107
复制
发表时间：
2010-02-16
影响因子：
11.1
通讯作者：
Oldstone, Michael B. A.
中科院分区：
文献类型：
--
作者：
Brooks, David G.;Walsh, Kevin B.;Oldstone, Michael B. A.
建立有效的T细胞应答对于在病毒感染和疫苗接种后引发持久免疫至关重要。感染后诱导了大量的抑制和刺激因子，正是这些信号的汇编定量和定性地编程了随后的效应和记忆T细胞应答。在淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染的反应中，免疫抑制细胞因子IL-10迅速上调;然而，IL-10如何调节通常被认为是“最佳”的免疫应答尚不清楚。我们证明，IL-10直接抑制效应和记忆CD 4 T细胞反应后，急性解决病毒感染。IL-10的阻断增强了效应CD 4 T细胞的大小和功能能力，这转化为增加和更有效的记忆反应。另一方面，缺乏IL-10信号传导并不影响记忆性CD 8 T细胞的发育。我们认为IL-10的阻断可能是一种有效的佐剂，可以特异性地增强CD 4 T细胞免疫和疫苗接种后的保护。
Mounting effective T cell responses is critical for eliciting long-lasting immunity following viral infection and vaccination. A multitude of inhibitory and stimulatory factors are induced following infection, and it is the compilation of these signals that quantitatively and qualitatively program the ensuing effector and memory T cell response. In response to lymphocytic choriomeningitis virus ( LCMV) infection, the immunosuppressive cytokine IL-10 is rapidly up-regulated; however, how IL-10 is regulating what is often considered an "optimal" immune response is unclear. We demonstrate that IL-10 directly inhibits effector and memory CD4 T cell responses following an acutely resolved viral infection. Blockade of IL-10 enhanced the magnitude and the functional capacity of effector CD4T cells that translated into increased and more effective memory responses. On the other hand, lack of IL-10 signaling did not impact memory CD8 T cell development. We propose that blockade of IL-10 may be an effective adjuvant to specifically enhance CD4 T cell immunity and protection following vaccination.