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

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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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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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