1. A functional subset of CD8+ T cells during chronic exhaustion is defined by SIRPα expression
- Author
-
Michal Caspi Tal, Aaron B. Carmody, Kim J. Hasenkrug, Matthew M Staron, Cesar J. Lopez Angel, Gunsagar S. Gulati, Mark M. Davis, Rahul Sinha, Edward A. Pham, Maxim Markovic, Benjamin Fram, Ying Ying Yiu, Susan M. Kaech, Jeffrey S. Glenn, Irving L. Weissman, Aijaz Ahmed, Lara Myers, Ronald J. Messer, Aaron M. Newman, and Laughing Bear Torrez Dulgeroff
- Subjects
0301 basic medicine ,Science ,Transgene ,General Physics and Astronomy ,02 engineering and technology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Retrovirus ,Cytotoxic T cell ,Receptor ,lcsh:Science ,Multidisciplinary ,biology ,Chemistry ,CD47 ,General Chemistry ,021001 nanoscience & nanotechnology ,biology.organism_classification ,3. Good health ,Cell biology ,Cytolysis ,030104 developmental biology ,lcsh:Q ,0210 nano-technology ,Clone (B-cell biology) ,CD8 - 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.
- Published
- 2019
- Full Text
- View/download PDF