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

Heng Giap Woon, Asolina Braun, Jane Li, Corey Smith, Jarem Edwards, Frederic Sierro, Carl G. Feng, Rajiv Khanna, Michael Elliot, Andrew Bell, Andrew D. Hislop, Stuart G. Tangye, Alan B. Rickinson, Thomas Gebhardt, Warwick J. Britton, Umaimainthan Palendira

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Abstract

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.

Original languageEnglish
Article numbere1005799
Number of pages19
JournalPLoS Pathogens
Volume12
Issue number8
DOIs
Publication statusPublished - 19 Aug 2016
Externally publishedYes

Keywords

  • T cells
  • cytotoxic T cells
  • tonsils
  • spleen
  • memory T cells
  • flow cytometry
  • viral replication
  • cytokines

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