TY - JOUR
T1 - Progenitor and terminal subsets of CD8+ T cells cooperate to contain chronic viral infection
AU - Paley, Michael A.
AU - Kroy, Daniela C.
AU - Odorizzi, Pamela M.
AU - Johnnidis, Jonathan B.
AU - Dolfi, Douglas V.
AU - Barnett, Burton E.
AU - Bikoff, Elizabeth K.
AU - Robertson, Elizabeth J.
AU - Lauer, Georg M.
AU - Reiner, Steven L.
AU - Wherry, E. John
PY - 2012/11/30
Y1 - 2012/11/30
N2 - Chronic infections strain the regenerative capacity of antiviral T lymphocyte populations, leading to failure in long-term immunity. The cellular and molecular events controlling this regenerative capacity, however, are unknown. We found that two distinct states of virus-specific CD8+ T cells exist in chronically infected mice and humans. Differential expression of the T-box transcription factors T-bet and Eomesodermin (Eomes) facilitated the cooperative maintenance of the pool of antiviral CD8+ T cells during chronic viral infection. T-bethi cells displayed low intrinsic turnover but proliferated in response to persisting antigen, giving rise to Eomeshi terminal progeny. Genetic elimination of either subset resulted in failure to control chronic infection, which suggests that an imbalance in differentiation and renewal could underlie the collapse of immunity in humans with chronic infections.
AB - Chronic infections strain the regenerative capacity of antiviral T lymphocyte populations, leading to failure in long-term immunity. The cellular and molecular events controlling this regenerative capacity, however, are unknown. We found that two distinct states of virus-specific CD8+ T cells exist in chronically infected mice and humans. Differential expression of the T-box transcription factors T-bet and Eomesodermin (Eomes) facilitated the cooperative maintenance of the pool of antiviral CD8+ T cells during chronic viral infection. T-bethi cells displayed low intrinsic turnover but proliferated in response to persisting antigen, giving rise to Eomeshi terminal progeny. Genetic elimination of either subset resulted in failure to control chronic infection, which suggests that an imbalance in differentiation and renewal could underlie the collapse of immunity in humans with chronic infections.
UR - http://www.scopus.com/inward/record.url?scp=84870230232&partnerID=8YFLogxK
U2 - 10.1126/science.1229620
DO - 10.1126/science.1229620
M3 - Article
C2 - 23197535
AN - SCOPUS:84870230232
SN - 0036-8075
VL - 338
SP - 1220
EP - 1225
JO - Science
JF - Science
IS - 6111
ER -