PD-1hi CD8+ resident memory T cells balance immunity and fibrotic sequelae

Zheng Wang, Shaohua Wang, Nick P. Goplen, Chaofan Li, In Su Cheon, Qigang Dai, Su Huang, Jinjun Shan, Chaoyu Ma, Zhenqing Ye, Min Xiang, Andrew H. Limper, Eva Carmona Porquera, Jacob E. Kohlmeier, Mark H. Kaplan, Nu Zhang, Aaron J. Johnson, Robert Vassallo, Jie Sun

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

CD8+ tissue-resident memory T (TRM) cells provide frontline immunity in mucosal tissues. The mechanisms regulating CD8+ TRM maintenance, heterogeneity, and protective and pathological functions are largely elusive. Here, we identify a population of CD8+ TRM cells that is maintained by major histocompatibility complex class I (MHC-I) signaling, and CD80 and CD86 costimulation after acute influenza infection. These TRM cells have both exhausted-like phenotypes and memory features and provide heterologous immunity against secondary infection. PD-L1 blockade after the resolution of primary infection promotes the rejuvenation of these exhausted-like TRM cells, restoring protective immunity at the cost of promoting postinfection inflammatory and fibrotic sequelae. Thus, PD-1 serves to limit the pathogenic capacity of exhausted-like TRM cells at the memory phase. Our data indicate that TRM cell exhaustion is the result of a tissue-specific cellular adaptation that balances fibrotic sequelae with protective immunity.

Original languageEnglish (US)
Article numbereaaw1217
JournalScience Immunology
Volume4
Issue number36
DOIs
StatePublished - Jan 1 2019

ASJC Scopus subject areas

  • Immunology and Allergy

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