Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Viral Immunol. 2010 Jun;23(3):285-94. doi: 10.1089/vim.2009.0110.
Impaired antiviral CD8 and CD4 T-cell responses are often associated with chronic viral infections. Cell-intrinsic as well as cell-extrinsic mechanisms are thought to dampen such responses, for example programmed death 1 receptor (PD-1) expression on T cells, and interleukin (IL)-10 production primarily by dendritic cells (DCs), have been shown to support viral persistence by suppressing immune responses. Here we demonstrate that CD103, an alpha E integrin necessary for T-cell homing and retention in the gut and other epithelia expressed by the majority of naïve CD8(+), and CD4(+)CD25(+) T cells and some DC subsets, is unnecessary for controlling T-cell responses during chronic lymphocytic choriomeningitis virus clone 13 (LCMV cl13) infection. T-cell analysis following viral infection showed that the primary as well as the memory CD8(+) and CD4(+) T-cell responses among CD103-sufficient and CD103-deficient mice were identical. In addition, no rescue of cytokine production by virus-specific T cells or alterations in viral titers in the absence of intrinsic CD103 expression was observed. Interestingly, CD103 levels on the effector CD8(+) T cells became reduced soon after virus infection, with a small proportion of cells co-expressing PD-1 and CD103. In contrast, although no substantial differences in the frequency and number of the CD4(+)CD25(+) cell population were seen, CD103 expression increased significantly over time in this population, correlating with viral persistence. Thus, a lack of CD103 expression does not affect functional impairment of effector T-cell responses during chronic viral infection.
抗病毒的 CD8 和 CD4 T 细胞反应受损通常与慢性病毒感染有关。细胞内和细胞外机制被认为会抑制这种反应,例如 T 细胞上程序性死亡 1 受体 (PD-1) 的表达,以及主要由树突状细胞 (DC) 产生的白细胞介素 (IL)-10,已被证明通过抑制免疫反应来支持病毒的持续存在。在这里,我们证明 CD103,一种对于 T 细胞归巢和在肠道和其他上皮组织中的保留至关重要的 αE 整合素,在大多数幼稚 CD8(+)和 CD4(+)CD25(+)T 细胞和一些 DC 亚群中表达,对于控制慢性淋巴细胞脉络丛脑膜炎病毒克隆 13 (LCMV cl13) 感染期间的 T 细胞反应是不必要的。病毒感染后的 T 细胞分析表明,在 CD103 充足和 CD103 缺乏的小鼠中,主要的和记忆性 CD8(+)和 CD4(+)T 细胞反应是相同的。此外,在没有固有 CD103 表达的情况下,未观察到病毒特异性 T 细胞的细胞因子产生的恢复或病毒滴度的改变。有趣的是,在病毒感染后,效应 CD8(+)T 细胞上的 CD103 水平很快降低,一小部分细胞同时表达 PD-1 和 CD103。相比之下,尽管在 CD4(+)CD25(+)细胞群中观察到频率和数量没有明显差异,但该细胞群中的 CD103 表达随着时间的推移显著增加,与病毒持续存在相关。因此,缺乏 CD103 表达不会影响慢性病毒感染期间效应 T 细胞反应的功能受损。