Seddiki Nabila, Brezar Vedran, Draenert Rika
aInserm bFaculté de médecine, Université Paris Est cVaccine Research Institute, Créteil, France dMedizinische Klinik IV, Klinikum der Universität München, Munich, Germany *Dr Nabila Seddiki and Vedran Brezar contributed equally to the writing of this article.
Curr Opin HIV AIDS. 2014 Sep;9(5):452-8. doi: 10.1097/COH.0000000000000087.
Suppressor cells regulate immune responses during chronic viral infection by limiting immunopathology associated with inflammation and immune activation. This dampening of adaptive immune responses can be harmful in HIV-1 infection as it also prevents the immune system from clearing the virus, leading to viral persistence and prolonged antigen expression that often leads to immune exhaustion. A current priority is to find the best strategy to target and manipulate key molecules such as CD39 that suppress anti-HIV-1 immune responses.
New suppressor cell subsets and cellular markers have been identified and characterized in the past years. We are able to identify and measure regulatory T cells, regulatory B cells and myeloid-derived suppressor cells in HIV-1-infected patients. We can also measure antigen-specific regulatory T cells in patients, which is a valuable step forward. Targeting HIV-1-specific regulatory T cells could be beneficial if we aim to manipulate key inhibitory molecules such as CTLA-4 and/or PD-1 that have already proven their efficacy in cancer. New other possible targets to take into account are CD39 and Tim-3-Gal9 pathways that have recently attracted attention in the field. These new findings offer the possibility to recognize suppressor cells as future targets in therapeutic vaccines because it became obvious that good vaccines candidates should concurrently generate robust effector responses and inhibit specific pathways that lead to immune suppression and exhaustion.
The recent advances on suppressor cells and the availability of new markers or assays will certainly open up new avenues for targeting molecules that are involved in immune suppression pathways, thus avoiding viral persistence and immune exhaustion.
抑制性细胞通过限制与炎症和免疫激活相关的免疫病理反应来调节慢性病毒感染期间的免疫应答。在HIV-1感染中，这种适应性免疫应答的减弱可能是有害的，因为它也会阻止免疫系统清除病毒，导致病毒持续存在和抗原长期表达，进而常常导致免疫耗竭。当前的一个优先事项是找到最佳策略来靶向和操控诸如CD39等抑制抗HIV-1免疫应答的关键分子。
在过去几年中，已鉴定并表征了新的抑制性细胞亚群和细胞标志物。我们能够在HIV-1感染患者中鉴定和测量调节性T细胞、调节性B细胞和髓源性抑制细胞。我们还能测量患者体内抗原特异性调节性T细胞，这是向前迈出的有价值的一步。如果我们旨在操控诸如CTLA-4和/或PD-1等已在癌症中证明其疗效的关键抑制性分子，那么靶向HIV-1特异性调节性T细胞可能有益。其他需要考虑的新的可能靶点是最近在该领域引起关注的CD39和Tim-3-Gal9通路。这些新发现为将抑制性细胞识别为治疗性疫苗的未来靶点提供了可能性，因为很明显，优秀的疫苗候选物应同时产生强大的效应器应答并抑制导致免疫抑制和耗竭的特定通路。
抑制性细胞方面的最新进展以及新标志物或检测方法的可用性肯定会为靶向参与免疫抑制通路的分子开辟新途径，从而避免病毒持续存在和免疫耗竭。
