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Professional Memory CD4+ T Lymphocytes Preferentially Reside and Rest in the Bone Marrow
Open accessAbstract
CD4(+) T lymphocytes are key to immunological memory. Here we show that in the memory phase of specific immune responses, most of the memory CD4(+) T lymphocytes had relocated into the bone marrow (BM) within 3-8 weeks after their generation-a process involving integrin alpha2. Antigen-specific memory CD4(+) T lymphocytes highly expressed Ly-6C, unlike most splenic CD44(hi)CD62L(-) CD4(+) T lymphocytes. In adult mice, more than 80% of Ly-6C(hi)CD44(hi)CD62L(-) memory CD4(+) T lymphocytes were in the BM. In the BM, they associated to IL-7-expressing VCAM-1(+) stroma cells. Gene expression and proliferation were downregulated, indicating a resting state. Upon challenge with antigen, they rapidly expressed cytokines and CD154 and efficiently induced the production of high-affinity antibodies by B lymphocytes. Thus, in the memory phase of immunity, memory helper T cells are maintained in BM as resting but highly reactive cells in survival niches defined by IL-7-expressing stroma cells.
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“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 [243]
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Metadata
- Authors
- Tokoyoda, K., Zehentmeier, S., Hegazy, A. N., Albrecht, I., Grün, J. R., Löhning, M., & Radbruch, A.
- Affiliations
- German Rheumatism Research Centre (DE)
- Corresponding author
- Tokoyoda, Koji
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2009-05
- Volume
- 30
- Issue
- 5
- Pages
- 721-730
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2065708749
- Cited by
- 352
- References
- 48
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 4 · 2023: 4 · 2022: 11 · 2021: 18 · 2020: 15 · 2019: 31 · 2018: 27 · 2017: 24 · 2016: 27 · 2015: 22 · 2014: 23 · 2013: 32 · 2012: 22
- FWCI
- 13.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1538 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- 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 CD4+ T cells, bone marrow, T cell homing, integrin alpha2, Ly6C, CD44, L-selectin, IL-7, VCAM-1, stromal cells, T cell proliferation, CD154, antibody production, immunological memory
- MeSH terms
- Animals, Antigens, Ly, B-Lymphocytes, Bone Marrow, Immunologic Memory, CD4-Positive T-Lymphocytes, Down-Regulation, Interleukin-7, Gene Expression, Stromal Cells, Oligonucleotide Array Sequence Analysis, Integrin alpha2, Mice
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