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- Title
A functional subset of CD8<sup>+</sup> T cells during chronic exhaustion is defined by SIRPα expression.
- Authors
Myers, Lara M.; Tal, Michal Caspi; Torrez Dulgeroff, Laughing Bear; Carmody, Aaron B.; Messer, Ronald J.; Gulati, Gunsagar; Yiu, Ying Ying; Staron, Matthew M.; Angel, Cesar Lopez; Sinha, Rahul; Markovic, Maxim; Pham, Edward A.; Fram, Benjamin; Ahmed, Aijaz; Newman, Aaron M.; Glenn, Jeffrey S.; Davis, Mark M.; Kaech, Susan M.; Weissman, Irving L.; Hasenkrug, Kim J.
- Abstract
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 SIRPα, a protein not previously reported on lymphocytes. On SIRPα+ CD8+ T cells, expression of co-inhibitory receptors is counterbalanced by expression of co-stimulatory receptors and it is only SIRPα+ cells that actively proliferate, transcribe IFNγ and show cytolytic activity. Furthermore, target cells that express the ligand for SIRPα, CD47, are more susceptible to CD8+ T cell-killing in vivo. SIRPα+ 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 SIRPα+ CD8+ T cells. SIRPa is most commonly known as a phagocytosis inhibitory receptor expressed by myeloid cells. Here the authors show SIRPa is expressed on a subset of CD8+ T cells with higher proliferative and effector activity during the chronic phase of the immune response to viral infection.
- Publication
Nature Communications, 2019, Vol 10, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-019-08637-9