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

• Type of Material: Article
• Authors: Zheng Wang, Mayo Clinic; Shaohua Wang, Mayo Clinic; Nick P. Goplen, Mayo Clinic; Chaofan Li Li, Mayo Clinic; In Su Cheon, Mayo Clinic; Qigang Dai, Mayo Clinic; Su Huang, Mayo Clinic; Jinjun Shan, Nanjing University of Chinese Medicine; Chaoyu Ma, University of Texas San Antonio; Zhenqing Ye, Mayo Clinic; Min Xiang, Mayo Clinic; Andrew H. Limper, Mayo Clinic; Eva-Carmona Porquera, Mayo Clinic; Jacob Kohlmeier, Emory University; Mark H. Kaplan, Indiana University; Nu Zhang, University of Texas San Antonio; Aaron J. Johnson, Mayo Clinic; Robert Vassallo, Mayo Clinic; Jie Sun, Mayo Clinic
• Language: English
• Date: 2019-06-01
• Publisher: AMER ASSOC ADVANCEMENT SCIENCE
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
• Final Published Version (URL): http://dx.doi.org/10.1126/sciimmunol.aaw1217
• Title of Journal or Parent Work: SCIENCE IMMUNOLOGY
• Volume: 4
• Issue: 36
• Grant/Funding Information: This work was supported by grants from NIH RO1 AI112844, RO1 AG047156, and RO1 HL126647 to J.S.; T32AG049672 to N.P.G.; R01 HL62150 and NHLBI contract 268201600004I-0–26800001-1 to A.H.L.; R01 AI057459 and R01 AI129241 to M.H.K.; R56 NS094150 and R01 NS103212 to A.J.J.; RO1 AI125701 and R21 AI139721 to N.Z.; R01HL122559 to J.E.K.; Huvis Foundation grant to R.V.; Mayo Clinic Kogod Aging Center Pilot grant and Mayo Clinic Center for Biomedical Discovery discretionary fund to J.S.; and CRI (Cancer Research Institute) Clinic and Laboratory Integration Program to N. Z.
• Keywords: PROMOTES; Science & Technology; INFLUENZA-VIRUS INFECTION; ANTIGEN PRESENTATION; EXPRESSION; PROTECTION; Life Sciences & Biomedicine; PERSISTENCE; IDIOPATHIC PULMONARY-FIBROSIS; Immunology; EFFECTOR; CD28; DENDRITIC CELLS

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.