Professional Memory CD4+ T Lymphocytes Preferentially Reside and Rest in the Bone Marrow

Tokoyoda, Koji; Zehentmeier, Sandra; Hegazy, Ahmed N.; Albrecht, Inka; Grün, Joachim R.; Löhning, Max; Radbruch, Andreas

doi:10.1016/j.immuni.2009.03.015

Cited by 352T-cell and B-cell ImmunologyImmunotherapy and Immune ResponsesImmune responses and vaccinations

Professional Memory CD4+ T Lymphocytes Preferentially Reside and Rest in the Bone Marrow

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Tokoyoda, Koji, Zehentmeier, Sandra, Hegazy, Ahmed N., Albrecht, Inka, Grün, Joachim R., Löhning, Max, Radbruch, Andreas·2009·Immunity

DOI 10.1016/j.immuni.2009.03.015

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Abstract

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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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 [243]

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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: Tokoyoda, Koji
Zehentmeier, Sandra
Hegazy, Ahmed N.
Albrecht, Inka
Grün, Joachim R.
Löhning, Max
Radbruch, Andreas
Venue: Immunity
Publisher: Elsevier BV
Published: 2009-05
Volume: 30
Issue: 5
Pages: 721-730
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2009.03.015
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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Professional Memory CD4+ T Lymphocytes Preferentially Reside and Rest in the Bone Marrow

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