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Proliferating Transitory T Cells with an Effector-like Transcriptional Signature Emerge from PD-1+ Stem-like CD8+ T Cells during Chronic Infection.

Authors
  • Hudson, William H1
  • Gensheimer, Julia1
  • Hashimoto, Masao1
  • Wieland, Andreas1
  • Valanparambil, Rajesh M1
  • Li, Peng2
  • Lin, Jian-Xin2
  • Konieczny, Bogumila T1
  • Im, Se Jin1
  • Freeman, Gordon J3
  • Leonard, Warren J2
  • Kissick, Haydn T4
  • Ahmed, Rafi5
  • 1 Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30033, USA.
  • 2 Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1674, USA.
  • 3 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • 4 Department of Urology, Emory University School of Medicine, Atlanta, GA 30033, USA.
  • 5 Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30033, USA. Electronic address: [email protected]
Type
Published Article
Journal
Immunity
Publication Date
Nov 27, 2019
Identifiers
DOI: 10.1016/j.immuni.2019.11.002
PMID: 31810882
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

T cell dysfunction is a characteristic feature of chronic viral infection and cancer. Recent studies in chronic lymphocytic choriomeningitis virus (LCMV) infection have defined a PD-1+ Tcf-1+ CD8+ T cell subset capable of self-renewal and differentiation into more terminally differentiated cells that downregulate Tcf-1 and express additional inhibitory molecules such as Tim3. Here, we demonstrated that expression of the glycoprotein CD101 divides this terminally differentiated population into two subsets. Stem-like Tcf-1+ CD8+ T cells initially differentiated into a transitory population of CD101-Tim3+ cells that later converted into CD101+ Tim3+ cells. Recently generated CD101-Tim3+ cells proliferated in vivo, contributed to viral control, and were marked by an effector-like transcriptional signature including expression of the chemokine receptor CX3CR1, pro-inflammatory cytokines, and granzyme B. PD-1 pathway blockade increased the numbers of CD101-Tim3+ CD8+ T cells, suggesting that these newly generated transitional cells play a critical role in PD-1-based immunotherapy. Copyright © 2019 Elsevier Inc. All rights reserved.

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