Type II membrane protein CD69 regulates the formation of resting T-helper memory
Open accessAbstract
Memory T-helper (Th) lymphocytes are crucial for the maintenance of acquired immunity to eliminate infectious pathogens. We have previously demonstrated that most memory Th lymphocytes reside and rest on stromal niches of the bone marrow (BM). Little is known, however, regarding the molecular basis for the generation and maintenance of BM memory Th lymphocytes. Here we show that CD69-deficient effector CD4 T lymphocytes fail to relocate into and persist in the BM and therefore to differentiate into memory cells. Consequently, CD69-deficient CD4 T cells fail to facilitate the production of high-affinity antibodies and the generation of BM long-lived plasma cells in the late phase of immune responses. Thus, CD69 is critical for the generation and maintenance of professional memory Th lymphocytes, which can efficiently help humoral immunity in the late phase. The deficit of immunological memory in CD69-deficient mice also highlights the essential role of BM for the establishment of Th memory.
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Trm 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 [242]
The Results and Discussion describe CD69-dependent relocation of memory T-helper cells to bone marrow and their persistence on stromal cells. Our copy does not address defining Trm as independent populations through parabiosis, distinct transcriptional profiles or antigen-receptor repertoires, or persistence in transplanted tissues; searches for those terms found no supporting passage. (LLM, conf=0.76)
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Self-citation
- Authors
- Shinoda, K., Tokoyoda, K., Hanazawa, A., Hayashizaki, K., Zehentmeier, S., Hosokawa, H., Iwamura, C., Koseki, H., Tumes, D. J., Radbruch, A., & Nakayama, T.
- Affiliations
- Chiba University (JP)
- German Rheumatism Research Centre (DE)
- RIKEN (JP)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-04-02
- Volume
- 109
- Issue
- 19
- Pages
- 7409-7414
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3358871
- OpenAlex
- W2105955827
- Cited by
- 143
- References
- 37
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 7 · 2023: 4 · 2022: 9 · 2021: 16 · 2020: 5 · 2019: 9 · 2018: 9 · 2017: 8 · 2016: 15 · 2015: 12 · 2014: 11 · 2013: 11 · 2012: 4
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alexander von Humboldt-Stiftung
- Uehara Memorial Foundation
- Deutsche Forschungsgemeinschaft (SFB 650)
- Bundesministerium für Bildung und Forschung
- Astellas Pharma
- Astellas Foundation for Research on Metabolic Disorders
- Japan Society for the Promotion of Science (21390147, 23890030, 23790522, 23659240, 22591093, 22689014)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- CD69, CD4+ T cells, immunological memory, humoral immunity, long-lived plasma cells, type II membrane protein, T cell homing
- MeSH terms
- CD69 Antigens, Animals, Antigens, Differentiation, T-Lymphocyte, B-Lymphocytes, Bone Marrow, Bone Marrow Cells, Female, Flow Cytometry, T-Lymphocytes, Helper-Inducer, Immunologic Memory, Male, Membrane Proteins, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, CD4-Positive T-Lymphocytes, Antigens, CD, Mice, SCID, Stromal Cells, Mice, Knockout, Microscopy, Confocal, Adoptive Transfer, Lectins, C-Type, Green Fluorescent Proteins, Mice
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