A functional subset of CD8+ T cells during chronic exhaustion is defined by SIRPα expression View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Lara M. Myers, Michal Caspi Tal, Laughing Bear Torrez Dulgeroff, Aaron B. Carmody, Ronald J. Messer, Gunsagar Gulati, Ying Ying Yiu, Matthew M. Staron, Cesar Lopez Angel, Rahul Sinha, Maxim Markovic, Edward A. Pham, Benjamin Fram, Aijaz Ahmed, Aaron M. Newman, Jeffrey S. Glenn, Mark M. Davis, Susan M. Kaech, Irving L. Weissman, Kim J. Hasenkrug

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. More... »

PAGES

794

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-019-08637-9

DOI

http://dx.doi.org/10.1038/s41467-019-08637-9

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112165473

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30770827


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