A functional subset of CD8+ T cells during chronic exhaustion is defined by SIRP? expression.

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 SIRP?, a protein not previously reported on lymphocytes. On SIRP?+ CD8+ T cells, expression of co-inhibitory receptors is counterbalanced by expression of co-stimulatory receptors and it is only SIRP?+ cells that actively proliferate, transcribe IFN? and show cytolytic activity. Furthermore, target cells that express the ligand for SIRP?, CD47, are more susceptible to CD8+ T cell-killing in vivo. SIRP?+ 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 SIRP?+ CD8+ T cells.

SUBMITTER: Myers LM 

PROVIDER: S-EPMC6377614 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature