CD160 and PD-1 Co-Expression on HIV-Specific CD8 T Cells Defines a Subset with Advanced Dysfunction

Chronic viral infections lead to persistent cd8 t cell activation and functional exhaustion. expression of programmed cell death-1 (pd-1) has been associated to cd8 t cell dysfunction in hiv infection. herein we report that another negative regulator of t cell activation,cd160,was also upregulated on hiv-specific cd8 t lymphocytes mostly during the chronic phase of infection. cd8 t cells that expressed cd160 or pd-1 were still functional whereas co-expression of cd160 and pd-1 on cd8 t cells defined a novel subset with all the characteristics of functionally exhausted t cells. blocking the interaction of cd160 with hvem,its natural ligand,increased hiv-specific cd8 t cell proliferation and cytokine production. transcriptional profiling showed that cd160-pd-1+cd8 t cells encompassed a subset of cd8+ t cells with activated transcriptional programs,while cd160+pd-1+ t cells encompassed primarily cd8+ t cells with an exhausted phenotype. the transcriptional profile of cd160+pd-1+ t cells showed the downregulation of the nfκb transcriptional node and the upregulation of several inhibitors of t cell survival and function. overall,we show that cd160 and pd-1 expressing subsets allow differentiating between activated and exhausted cd8 t cells further reinforcing the notion that restoration of function will require multipronged approaches that target several negative regulators. © 2012 peretz et al.