Lund Jennifer M, Hsing Lianne, Pham Thuy T, Rudensky Alexander Y
Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
Science. 2008 May 30;320(5880):1220-4. doi: 10.1126/science.1155209. Epub 2008 Apr 24.
Suppression of immune responses by regulatory T cells (Tregs) is thought to limit late stages of pathogen-specific immunity as a means of minimizing associated tissue damage. We examined a role for Tregs during mucosal herpes simplex virus infection in mice, and observed an accelerated fatal infection with increased viral loads in the mucosa and central nervous system after ablation of Tregs. Although augmented interferon production was detected in the draining lymph nodes (dLNs) in Treg-deprived mice, it was profoundly reduced at the infection site. This was associated with a delay in the arrival of natural killer cells, dendritic cells, and T cells to the site of infection and a sharp increase in proinflammatory chemokine levels in the dLNs. Our results suggest that Tregs facilitate early protective responses to local viral infection by allowing a timely entry of immune cells into infected tissue.
调节性T细胞(Tregs)对免疫反应的抑制作用被认为是限制病原体特异性免疫的后期阶段,以此将相关组织损伤降至最低。我们研究了Tregs在小鼠黏膜单纯疱疹病毒感染过程中的作用,发现Tregs缺失后,小鼠会出现加速的致命感染,黏膜和中枢神经系统中的病毒载量增加。虽然在Treg缺失的小鼠引流淋巴结(dLNs)中检测到干扰素产生增加,但在感染部位却显著减少。这与自然杀伤细胞、树突状细胞和T细胞到达感染部位的延迟以及dLNs中促炎趋化因子水平的急剧增加有关。我们的结果表明,Tregs通过允许免疫细胞及时进入感染组织,促进对局部病毒感染的早期保护性反应。