Progenitor and Terminal Subsets of CD8 + T Cells Cooperate to Contain Chronic Viral Infection

• DOI: 10.1126/science.1229620
• Publication Date: 2012-11-29T19:15:18Z
• Authors: Michael A. Paley; Daniela C. Kroy; Pamela M. Odorizzi; Jonathan B. Johnn...; Douglas V. Dolfi; Burton E. Barnett; Elizabeth K. Bikoff; Elizabeth J. Robe...; Georg M. Lauer; Steven L. Reiner; E. John Wherry
• Keywords: Chronic infection; Progenitor; Viral infection; Cellular immunity

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 capacity, however, are unknown. We found that two distinct states virus-specific CD8(+) cells exist chronically infected mice humans. Differential expression T-box transcription factors T-bet Eomesodermin (Eomes) facilitated cooperative maintenance pool during chronic viral infection. T-bet(hi) displayed low intrinsic turnover but proliferated response persisting antigen, giving rise Eomes(hi) terminal progeny. Genetic elimination either subset resulted control infection, which suggests an imbalance differentiation renewal could underlie collapse immunity humans with infections.