Resident memory CD4⁺ T lymphocytes mobilize from bone marrow to contribute to a systemic secondary immune reaction

Carla Cendón¹, Weijie Du¹, Pawel Durek¹, Yuk-Chien Liu¹, Tobias Alexander², Lindsay Serene³, Xinyi Yang⁴, Gilles Gasparoni⁵, Abdulrahman Salhab⁵, Karl Nordström⁵, Tina Lai¹, Axel R Schulz⁶, Anna Rao¹, Gitta A Heinz⁷, Ana L Stefanski², Anne Claußnitzer², Katherina Siewert⁸, Thomas Dörner², Hyun-Dong Chang^{1

9}, Hans-Dieter Volk^{10

11}, Chiara Romagnani^{12

13}, Zhihai Qin^{14

15}, Sebastian Hardt¹⁶, Carsten Perka¹⁶, Simon Reinke¹¹, Jörn Walter⁵, Mir-Farzin Mashreghi^{7

11}, Kevin Thurley^{17

18}, Andreas Radbruch¹, Jun Dong¹

Affiliations

¹ Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany.
² Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
³ Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USA.
⁴ Otto-Warburg-Laboratory, Computational Epigenomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
⁵ Department of Genetics, University of Saarland (UdS), Saarbrücken, Germany.
⁶ Mass Cytometry, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany.
⁷ Therapeutic Gene Regulation, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany.
⁸ Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, Berlin, Germany.
⁹ Schwiete-Laboratory for Microbiota and Inflammation, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany.
¹⁰ Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹¹ BIH Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹² Innate Immunity, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany.
¹³ Medical Department/Gastroenterology, Infectiology and Rheumatology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹⁴ Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Bejing, P. R. China.
¹⁵ Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, P. R. China.
¹⁶ Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹⁷ Systems Biology of Inflammation, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany.
¹⁸ Institute for Theoretical Biology, Humboldt University, Berlin, Germany.

PMID: 35245389
DOI: 10.1002/eji.202149726

Free article

Resident memory CD4⁺ T lymphocytes mobilize from bone marrow to contribute to a systemic secondary immune reaction

Carla Cendón et al. Eur J Immunol. 2022 May.

Free article

. 2022 May;52(5):737-752.

doi: 10.1002/eji.202149726. Epub 2022 Mar 14.

Authors

Affiliations

¹ Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany.
² Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
³ Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USA.
⁴ Otto-Warburg-Laboratory, Computational Epigenomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
⁵ Department of Genetics, University of Saarland (UdS), Saarbrücken, Germany.
⁶ Mass Cytometry, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany.
⁷ Therapeutic Gene Regulation, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany.
⁸ Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, Berlin, Germany.
⁹ Schwiete-Laboratory for Microbiota and Inflammation, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany.
¹⁰ Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹¹ BIH Center for Regenerative Therapies (BCRT), Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹² Innate Immunity, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany.
¹³ Medical Department/Gastroenterology, Infectiology and Rheumatology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹⁴ Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Bejing, P. R. China.
¹⁵ Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, P. R. China.
¹⁶ Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.
¹⁷ Systems Biology of Inflammation, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany.
¹⁸ Institute for Theoretical Biology, Humboldt University, Berlin, Germany.

PMID: 35245389
DOI: 10.1002/eji.202149726

Abstract

Resident memory T lymphocytes (T_RM ) of epithelial tissues and the Bm protect their host tissue. To what extent these cells are mobilized and contribute to systemic immune reactions is less clear. Here, we show that in secondary immune reactions to the measles-mumps-rubella (MMR) vaccine, CD4⁺ T_RM are mobilized into the blood within 16 to 48 h after immunization in humans. This mobilization of T_RM is cognate: T_RM recognizing other antigens are not mobilized, unless they cross-react with the vaccine. We also demonstrate through methylome analyses that T_RM are mobilized from the Bm. These mobilized cells make significant contribution to the systemic immune reaction, as evidenced by their T-cell receptor Vβ clonotypes represented among the newly generated circulating memory T-cells, 14 days after vaccination. Thus, T_RM of the Bm confer not only local, but also systemic immune memory.

Keywords: Bm Trm cells; T-cell receptor repertoire; epigenetic signature; mobilization; systemic memory.

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References

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Resident memory CD4⁺ T lymphocytes mobilize from bone marrow to contribute to a systemic secondary immune reaction

Affiliations

Resident memory CD4⁺ T lymphocytes mobilize from bone marrow to contribute to a systemic secondary immune reaction

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Abstract

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Medical

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