PDF(Pubmed)
Abstract：
Retroviral envelope (Env) proteins have long been recognized to exhibit immunosuppressive properties, which affect the CD8+ T-cell response to an infection but also to immunization. Interestingly, we previously showed in the Friend murine leukemia virus (F-MuLV) model that the surface Env protein gp70 also plays a role in immunosuppression, in addition to the immunosuppressive function attributed to the transmembrane Env protein. We now demonstrate that immunization with F-MuLV Env leads to a significant increase in interleukin-10 (IL-10)-producing CD4+ T cells and that the induction of CD8+ T-cell responses in the presence of Env is rescued if the capacity of CD4+ T cells to produce IL-10 is abrogated, indicating a mechanistic role of IL-10-producing CD4+ T cells in mediating the Env-induced suppression of CD8+ T-cell responses in Env co-immunization. We found that CD8+ T-cell responses against different immunogens are not all equally affected. On the other hand, suppression of immunity was observed not only in co-immunization experiments but also for immune control of subcutaneous tumor growth after an Env immunization. Finally, we show that suppression of CD8+ T cells by the surface Env protein is observed not only for Friend MuLV Env but also for the Env proteins of other gamma retroviruses. Taken together, our results show that IL-10-producing CD4+ T cells mechanistically underlie the Env-mediated suppression of CD8+ T-cell responses and suggest the presence of an immunosuppressive motif in the surface Env protein of gamma retroviruses.
摘要：
逆转录病毒包膜（Env）蛋白长期以来被认为具有免疫抑制特性，影响CD8+T细胞对感染的反应，也影响免疫。有趣的是,我们先前在Friend鼠白血病病毒（F-MuLV）模型中显示，表面Env蛋白gp70也在免疫抑制中起作用，除了归因于跨膜Env蛋白的免疫抑制功能。我们现在证明，用F-MuLVEnv免疫导致产生白细胞介素-10（IL-10）的CD4+T细胞显着增加，并且如果CD4+T细胞产生IL-10的能力被废除，则在Env存在下诱导CD8+T细胞应答被挽救。表明在Env共免疫中产生IL-10的CD4+T细胞在介导Env诱导的CD8+T细胞应答抑制中的机制作用。我们发现针对不同免疫原的CD8+T细胞应答并不都同样受到影响。另一方面,免疫抑制不仅在共免疫实验中观察到,而且对于Env免疫后皮下肿瘤生长的免疫控制也观察到。最后,我们表明，不仅在FriendMuLVEnv而且在其他γ逆转录病毒的Env蛋白中观察到表面Env蛋白对CD8T细胞的抑制。一起来看,我们的结果表明,产生IL-10的CD4+T细胞在机制上是Env介导的CD8+T细胞应答抑制的基础,并提示γ逆转录病毒表面Env蛋白中存在免疫抑制基序.
