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

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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.