Die Rolle von inhibitorischen Rezeptoren und deren Liganden bei der Immunflucht vor zytotoxischen CD8+ T-Zellen und bei der Etablierung einer chronischen Virusinfektion (B08)

项目B8的PI描述了PD-L1在逆转录病毒感染的细胞上上调，并介导了细胞毒CD8+T细胞的逃逸和随后的功能障碍。在慢性FV感染期间，阻断PD-L1可以增强CD8+T细胞的反应，但更有效的是联合治疗，同时阻断抑制性受体和耗尽Tregs。然而，在急性逆转录病毒感染期间，这种联合治疗会导致致命的免疫病理学。MDSCs代表一个细胞免疫检查点，可以控制特定的T细胞反应。Pi Zelinsky将结合MDSC耗尽和PDL-1阻断作为新的联合疗法，该疗法可能在不引发免疫病理的情况下限制急性和慢性FV和HIV感染。他还将研究慢性病毒感染期间抑制性受体、Tregs和MDSCs之间的代偿机制。

The PI of project B8 described that PD-L1 is up-regulated on retrovirus-infected cells and mediates escape and subsequent dysfunction of cytotoxic CD8+ T cells. Blocking PD-L1 augments CD8+ T cell responses during chronic FV infection, but even more potent is a combination therapy blocking the inhibitory receptor and depleting Tregs at the same time. However, this combination therapy induces lethal immunopathology during an acute retroviral infection. MDSCs represent a cellular immune checkpoint that can control specific T cell responses. PI Zelinskyy will combine MDSC depletion and a PDL-1 block as novel combination therapy that may restrict acute and chronic FV and HIV infection without inducing immunopathology. He will also study the compensatory mechanisms between inhibitory receptors, Tregs and MDSCs during chronic viral infections.