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

• Published in: Science immunology 2019-06, Vol.4 (36)
• Main Authors: Wang, Zheng, Wang, Shaohua, Goplen, Nick P, Li, Chaofan, Cheon, In Su, Dai, Qigang, Huang, Su, Shan, Jinjun, Ma, Chaoyu, Ye, Zhenqing, Xiang, Min, Limper, Andrew H, Porquera, Eva-Carmona, Kohlmeier, Jacob E, Kaplan, Mark H, Zhang, Nu, Johnson, Aaron J, Vassallo, Robert, Sun, Jie
• Format: Article
• Language: English
• Subjects: Animals; B7-H1 Antigen - immunology; CD8-Positive T-Lymphocytes - immunology; Female; Fibrosis; Humans; Immunologic Memory; Influenza A virus; Lung - immunology; Lung - pathology; Lung Diseases, Interstitial - immunology; Male; Mice, Inbred C57BL; Mice, Transgenic; Orthomyxoviridae Infections - immunology; Programmed Cell Death 1 Receptor - immunology
• ISSN: 2470-9468; 2470-9468
• DOI: 10.1126/sciimmunol.aaw1217

CD8 tissue-resident memory T (T ) cells provide frontline immunity in mucosal tissues. The mechanisms regulating CD8 T maintenance, heterogeneity, and protective and pathological functions are largely elusive. Here, we identify a population of CD8 T cells that is maintained by major histocompatibility complex class I (MHC-I) signaling, and CD80 and CD86 costimulation after acute influenza infection. These T 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 T 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 T cells at the memory phase. Our data indicate that T cell exhaustion is the result of a tissue-specific cellular adaptation that balances fibrotic sequelae with protective immunity.