| First Author | Myers LM | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 794 |
| PubMed ID | 30770827 | Mgi Jnum | J:276685 |
| Mgi Id | MGI:6287060 | Doi | 10.1038/s41467-019-08637-9 |
| Citation | Myers LM, et al. (2019) A functional subset of CD8(+) T cells during chronic exhaustion is defined by SIRPalpha expression. Nat Commun 10(1):794 |
| abstractText | 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. |
