Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs
Open accessAbstract
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.
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A subset of Trm are confined to the CCR7−CD45RA+ TEMRA CD8+ T cells from tonsils, spleen, and bone marrow.
“A subset of Trm are also confined to the CCR7−CD45RA+ TEMRA CD8+ T cells from tonsils, spleen, and bone marrow [244, 265].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [265]
The Results section on CD69 expression reports that CD69+ CD8+ cells in tonsils and spleen occur in both TEM and TEMRA populations, not exclusively in TEMRA. The Results section on distinct memory subsets also identifies a tissue-resident-associated CD69+CD103+ subset that is uniformly CD45RA−CCR7−, rather than CD45RA+CCR7−. The reported analysis covers tonsils and spleen, not bone marrow; page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCD69-expressing cells can also be found in CD45RO− cells, especially in CD8+ T cells, which presumably consist of a subset of effector memory T cells re-expressing CD45RA (TEMRA).
“Additionally, CD69-expressing cells can also be found in CD45RO− cells, especially in CD8+ T cells, which presumably consist of a subset of effector memory T cells re-expresses CD45RA, also termed TEMRA [244, 265].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [265]
The Results section on CD69 expression (Fig. 1B; page unavailable) identifies CD69+ CD8+ cells in the CD45RA+ TEMRA subset of human spleens and tonsils. The paper measures CD45RA rather than CD45RO, however, and does not establish that CD69 expression in CD45RO− cells is especially prevalent among CD8+ cells compared with other T cells. (LLM, conf=0.84)
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References 55 · Cited by 97
- Authors
- 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.
- Affiliations
- The University of Sydney (AU)
- The University of Melbourne (AU)
- QIMR Berghofer Medical Research Institute (AU)
- University of Birmingham (GB)
- Garvan Institute of Medical Research (AU)
- Corresponding author
- Woon, Heng Giap
- Braun, Asolina
- Li, Jane
- Smith, Corey
- Edwards, Jarem
- Feng, Carl G.
- Khanna, Rajiv
- Elliot, Michael
- Bell, Andrew
- Hislop, Andrew D.
- Tangye, Stuart G.
- Rickinson, Alan B.
- Gebhardt, Thomas
- Britton, Warwick J.
- Palendira, Umaimainthan
- ORCID
- Venue
- PLOS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-08-19
- Volume
- 12
- Issue
- 8
- Pages
- e1005799
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC4991796
- OpenAlex
- W2508466388
- Cited by
- 97
- References
- 55
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 4 · 2023: 7 · 2022: 9 · 2021: 11 · 2020: 16 · 2019: 10 · 2018: 16 · 2017: 7 · 2016: 1 · 2013: 1
- FWCI
- 6.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion, cc-by)
- Funders
- National Health and Medical Research Council (1050471)
- Cancer Institute NSW (12/CDF/2-23)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- tissue-resident memory T cells, CD8+ T cells, compartmentalization, Epstein-Barr virus, cytomegalovirus, IL-15, sphingosine-1-phosphate receptor, KLF2, CD69, CD103, tonsil, spleen, T cell retention, chronic viral infection, gene expression profiling
- MeSH terms
- Cytomegalovirus Infections, Cytomegalovirus, Herpesvirus 4, Human, Female, Humans, Immunologic Memory, Male, Organ Specificity, Antigens, CD, CD8-Positive T-Lymphocytes, Interleukin-15, Epstein-Barr Virus Infections, Kruppel-Like Transcription Factors
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