TY  - JOUR
AU  - Woon, HG
AU  - Braun, A
AU  - Li, J
AU  - Smith, C
AU  - Edwards, J
AU  - Sierro, F
AU  - Feng, CG
AU  - Khanna, R
AU  - Elliot, M
AU  - Bell, A
AU  - Hislop, AD
AU  - Tangye, SG
AU  - Rickinson, AB
AU  - Gebhardt, T
AU  - Britton, WJ
AU  - Palendira, U
Y2  - 2021/02/05
Y1  - 2016/08/01
SN  - 1553-7366
UR  - http://hdl.handle.net/11343/260160
AB  - 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.
LA  - English
PB  - PUBLIC LIBRARY SCIENCE
T1  - Compartmentalization of Total and VirusSpecific Tissue-Resident Memory CD8+T Cells in Human Lymphoid Organs
DO  - 10.1371/journal.ppat.1005799
IS  - PLoS Pathogens
VL  - 12
IS  - 8
L1  - /bitstream/handle/11343/260160/PMC4991796.pdf?sequence=1&isAllowed=y
ER  -