Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs

PLoS Pathogens

Frederic Sierro¹  Heng Giap Woon¹  Jarem Edwards¹  Carl G. Feng¹  Andrew Bell²  Jane Li³  Asolina Braun³  Rajiv Khanna⁴  Thomas Gebhardt⁵  Corey Smith⁶  Michael Elliot⁶  Stuart G. Tangye⁷  Umaimainthan Palendira⁷  Alan B. Rickinson⁷  Warwick J. Britton⁸  Andrew D. Hislop⁹ 

[1] Centenary Institute, The University of Sydney, Newtown, New South Wales, Australia;Chris O’Brien Lifehouse Cancer Centre, Royal Prince Alfred Hospital, Camperdown, Sydney, New South Wales, Australia;Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia;Discipline of Infectious Diseases and Immunology, Sydney Medical School, The University of Sydney, Newtown, New South Wales, Australia;Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia;QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia;School of Cancer Sciences and MRC Centre for Immune Regulation, University of Birmingham, Edgbaston, United Kingdom;St Vincent’s Clinical School, University of New South Wales, Darlinghurst, New South Wales, Australia;Sydney Medical School, The University of Sydney, Newtown, New South Wales, Australia

关键词: T cells;    Cytotoxic T cells;    Tonsils;    Spleen;    Memory T cells;    Flow cytometry;    Viral replication;    Cytokines;   

DOI  :  10.1371/journal.ppat.1005799

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103—, and were retained within the spleen and tonsils in the absence of recent T cell stimulation. These two types of memory cells were distinct not only in their phenotype and transcriptional profile, but also in their anatomical localization within tonsils and spleen. The EBV-specific, but not CMV-specific, CD8+ memory T cells preferentially accumulated in the tonsils and acquired a phenotype that ensured their retention at the epithelial sites where EBV replicates. In vitro studies revealed that the cytokine IL-15 can potentiate the retention of circulating effector memory CD8+ T cells by down-regulating the expression of sphingosine-1-phosphate receptor, required for T cell exit from tissues, and its transcriptional activator, Kruppel-like factor 2 (KLF2). Within the tonsils the expression of IL-15 was detected in regions where CD8+ T cells localized, further supporting a role for this cytokine in T cell retention. Together this study provides evidence for the compartmentalization of distinct types of resident memory T cells that could contribute to the long-term protection against persisting viral infections.

【 授权许可】

CC BY