@article {549076,
	title = {Genetic absence of PD-1 promotes accumulation of terminally differentiated exhausted CD8+ T cells.},
	journal = {J Exp Med},
	volume = {212},
	number = {7},
	year = {2015},
	month = {2015 Jun 29},
	pages = {1125-37},
	abstract = {Programmed Death-1 (PD-1) has received considerable attention as a key regulator of CD8(+) T cell exhaustion during chronic infection and cancer because blockade of this pathway partially reverses T cell dysfunction. Although the PD-1 pathway is critical in regulating established "exhausted" CD8(+) T cells (TEX cells), it is unclear whether PD-1 directly causes T cell exhaustion. We show that PD-1 is not required for the induction of exhaustion in mice with chronic lymphocytic choriomeningitis virus (LCMV) infection. In fact, some aspects of exhaustion are more severe with genetic deletion of PD-1 from the onset of infection. Increased proliferation between days 8 and 14 postinfection is associated with subsequent decreased CD8(+) T cell survival and disruption of a critical proliferative hierarchy necessary to maintain exhausted populations long term. Ultimately, the absence of PD-1 leads to the accumulation of more cytotoxic, but terminally differentiated, CD8(+) TEX cells. These results demonstrate that CD8(+) T cell exhaustion can occur in the absence of PD-1. They also highlight a novel role for PD-1 in preserving TEX cell populations from overstimulation, excessive proliferation, and terminal differentiation.},
	keywords = {Adoptive Transfer, Animals, Bromodeoxyuridine, CD8-Positive T-Lymphocytes, Cell Differentiation, Cell Proliferation, Flow Cytometry, Lymphocytic Choriomeningitis, Mice, Programmed Cell Death 1 Receptor},
	issn = {1540-9538},
	doi = {10.1084/jem.20142237},
	author = {Odorizzi, Pamela M and Pauken, Kristen E and Paley, Michael A and Sharpe, Arlene and Wherry, E John}
}
