Quantifying Memory CD8 T Cells Reveals Regionalization of Immunosurveillance
Open accessAbstract
Memory CD8 T cells protect against intracellular pathogens by scanning host cell surfaces; thus, infection detection rates depend on memory cell number and distribution. Population analyses rely on cell isolation from whole organs, and interpretation is predicated on presumptions of near complete cell recovery. Paradigmatically, memory is parsed into central, effector, and resident subsets, ostensibly defined by immunosurveillance patterns but in practice identified by phenotypic markers. Because isolation methods ultimately inform models of memory T cell differentiation, protection, and vaccine translation, we tested their validity via parabiosis and quantitative immunofluorescence microscopy of a mouse memory CD8 T cell population. We report three major findings: lymphocyte isolation fails to recover most cells and biases against certain subsets, residents greatly outnumber recirculating cells within non-lymphoid tissues, and memory subset homing to inflammation does not conform to previously hypothesized migration patterns. These results indicate that most host cells are surveyed for reinfection by segregated residents rather than by recirculating cells that migrate throughout the blood and body.
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Both CD69+ and CD69− memory T cells of non-lymphoid tissues, like kidney and liver, are tissue resident.
“Through parabiosis experiments, it has been shown that both CD69+ and CD69− memory T cells of non-lymphoid tissues, like kidney and liver, are tissue resident [239].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [239]
The Results section, “CD69 is an imperfect marker of tissue residence” (page unavailable), reports CD69+ resident memory CD8 T cells in liver and kidney and says CD69− cells can also be resident there. The claim is too categorical: the paper says most CD69+ cells are resident, not all, and reports that only 35–60% of the marginated memory CD8 T-cell pool in the liver and kidney vascular compartments was resident. (LLM, conf=0.82)
Experimental — accuracy not yet measuredWhile the majority of Trm cells throughout different tissues constitutively express CD69, parabiosis and in vivo labeling experiments have highlighted that there are CD69− cells that reside long-term in tissues.
“While the majority of Trm cells throughout different tissues constitutively express CD69, parabiosis, and in vivo labeling experiments have highlighted that there are CD69− cells that reside long-term in tissues [239].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [239]
The Results section, “CD69 is an imperfect marker of tissue residence,” reports that CD69− cells can be functionally resident, using parabiosis and in vivo antibody labeling to assess residence. It does not establish that a majority of TRM across tissues express CD69: in the pancreas, salivary gland, and female reproductive tract, only 25–75% of memory P14 cells expressed it, although almost all were resident. (LLM, conf=0.88)
Experimental — accuracy not yet measuredTrm have been defined as independent populations by tissue retention in parabiosis experiments, by distinguishing transcriptional profiles, by exclusive Ag receptor repertoires and specificities, and by exclusive persistence in transplanted tissues.
“They have been defined as independent populations by tissue retention in parabiosis experiments [239, 240], by distinguishing transcriptional profiles [230, 241-245], by exclusive Ag receptor repertoires and specificities [243, 244, 246], and by exclusive persistence in transplanted tissues [247, 248].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [239]
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Self-citation
- Authors
- Steinert, E. M., Schenkel, J. M., Fraser, K. A., Beura, L. K., Manlove, L. S., Igyártó, B. Z., Southern, P. J., & Masopust, D.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Masopust, David
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 161
- Issue
- 4
- Pages
- 737-749
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4426972
- OpenAlex
- W1632859538
- Cited by
- 685
- References
- 46
- Citations by year
- 2026: 29 · 2025: 46 · 2024: 46 · 2023: 50 · 2022: 62 · 2021: 76 · 2020: 74 · 2019: 79 · 2018: 91 · 2017: 60 · 2016: 57 · 2015: 15
- FWCI
- 36.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (F31CA183226, P30CA077598)
- National Institute of Allergy and Infectious Diseases (R01AI084913, R01AI111671, R37AI084913, T32AI083196)
- National Institute of Diabetes and Digestive and Kidney Diseases (F30DK100159, F30-DK100159-02)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- memory CD8+ T cells, immune surveillance, parabiosis, lymphocyte isolation, tissue-resident memory T cells, effector memory T cells, central memory T cells, T cell migration, tissue inflammation, T cell differentiation, non-lymphoid tissues
- MeSH terms
- CD69 Antigens, Animals, Antigens, Differentiation, T-Lymphocyte, Arenaviridae Infections, Cell Movement, Immunologic Memory, Inflammation, Lymphocytic choriomeningitis virus, Mice, Inbred C57BL, Monitoring, Immunologic, Antigens, CD, T-Lymphocyte Subsets, CD8-Positive T-Lymphocytes, Lectins, C-Type, Mice
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