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Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs
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نویسنده
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woon h.g. ,braun a. ,li j. ,smith c. ,edwards j. ,sierro f. ,feng c.g. ,khanna r. ,elliot m. ,bell a. ,hislop a.d. ,tangye s.g. ,rickinson a.b. ,gebhardt t. ,britton w.j. ,palendira u.
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منبع
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plos pathogens - 2016 - دوره : 12 - شماره : 8
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چکیده
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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. © 2016 woon et al.
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آدرس
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centenary institute,the university of sydney,newtown,nsw, Australia, department of microbiology and immunology,the university of melbourne,the peter doherty institute for infection and immunity,melbourne,vic, Australia, department of microbiology and immunology,the university of melbourne,the peter doherty institute for infection and immunity,melbourne,vic, Australia, qimr berghofer medical research institute,brisbane,qld, Australia, centenary institute,the university of sydney,newtown,nsw, Australia, centenary institute,the university of sydney,newtown,nsw, Australia, centenary institute,the university of sydney,newtown,nsw,australia,discipline of infectious diseases and immunology,sydney medical school,the university of sydney,newtown,nsw, Australia, qimr berghofer medical research institute,brisbane,qld, Australia, chris o’brien lifehouse cancer centre,royal prince alfred hospital,camperdown,sydney,nsw,australia,sydney medical school,the university of sydney,newtown,nsw, Australia, school of cancer sciences and mrc centre for immune regulation,university of birmingham,edgbaston, United Kingdom, school of cancer sciences and mrc centre for immune regulation,university of birmingham,edgbaston, United Kingdom, garvan institute of medical research,darlinghurst,nsw,australia,st vincent’s clinical school,university of new south wales,darlinghurst,nsw, Australia, school of cancer sciences and mrc centre for immune regulation,university of birmingham,edgbaston, United Kingdom, department of microbiology and immunology,the university of melbourne,the peter doherty institute for infection and immunity,melbourne,vic, Australia, centenary institute,the university of sydney,newtown,nsw,australia,sydney medical school,the university of sydney,newtown,nsw, Australia, centenary institute,the university of sydney,newtown,nsw,australia,sydney medical school,the university of sydney,newtown,nsw, Australia
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Authors
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