Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 212, Issue 7, Pages 1125-1137Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20142237
Keywords
-
Categories
Funding
- T32 HIV Pathogenesis training grant
- Robertson Foundation/Cancer Research Institute Irvington Fellowship
- National Institutes of Health [AI105343, AI112521, AI117718, AI082630, AI095608, HHSN266200500030C]
Ask authors/readers for more resources
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 (T-EX 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(+) T-EX 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 T-EX cell populations from overstimulation, excessive proliferation, and terminal differentiation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available