Prolonged exposure of CD8+ T cells to antigenic stimulation, as in chronic viral infections, leads to a state of diminished function termed exhaustion. We now demonstrate that even during exhaustion there is a subset of functional CD8+ T cells defined by surface expression of SIRPalpha, a protein not previously reported on lymphocytes. On SIRPalpha+ CD8+ T cells, expression of co-inhibitory receptors is counterbalanced by expression of co-stimulatory receptors and it is only SIRPalpha+ cells that actively proliferate, transcribe IFNgamma and show cytolytic activity. Furthermore, target cells that express the ligand for SIRPalpha, CD47, are more susceptible to CD8+ T cell-killing in vivo. SIRPalpha+ CD8+ T cells are evident in mice infected with Friend retrovirus, LCMV Clone 13, and in patients with chronic HCV infections. Furthermore, therapeutic blockade of PD-L1 to reinvigorate CD8+ T cells during chronic infection expands the cytotoxic subset of SIRPalpha+ CD8+ T cells.
View details for PubMedID 30770827