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

Affiliation
Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany
Cendón, Carla;
Affiliation
Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany
Du, Weijie;
Affiliation
Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany
Durek, Pawel;
Affiliation
Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany
Liu, Yuk-Chien;
Affiliation
Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany
Alexander, Tobias;
Affiliation
Department of Biological Sciences, University of Notre Dame, Notre Dame, United States
Serene, Lindsay;
Affiliation
Otto-Warburg-Laboratory, Computational Epigenomics, Max Planck Institute for Molecular Genetics, Berlin, Germany
Yang, Xinyi;
Affiliation
Department of Genetics, University of Saarland (UdS), Saarbrücken, Germany
Gasparoni, Gilles;
Affiliation
Department of Genetics, University of Saarland (UdS), Saarbrücken, Germany
Salhab, Abdulrahman;
Affiliation
Department of Genetics, University of Saarland (UdS), Saarbrücken, Germany
Nordström, Karl;
Affiliation
Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany
Lai, Tina;
Affiliation
Mass Cytometry, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany
Schulz, Axel R.;
Affiliation
Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany
Rao, Anna;
Affiliation
Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany
Heinz, Gitta A.;
Affiliation
Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany
Stefanski, Ana L.;
Affiliation
Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany
Claußnitzer, Anne;
ORCID
0000-0003-0380-1594
Affiliation
German Federal Institute for Risk Assessment (BfR), Department 7 - Chemical and Product Safety, 7 SZ - Dermatotoxikology Study Centre, Berlin, Germany
Siewert, Katherina;
Affiliation
Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany
Dörner, Thomas;
Affiliation
Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany
Chang, Hyun-Dong;
Affiliation
Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany
Volk, Hans-Dieter;
Affiliation
Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany
Romagnani, Chiara;
Affiliation
Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Bejing, China
Qin, Zhihai;
Affiliation
Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany
Hardt, Sebastian;
Affiliation
Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany
Perka, Carsten;
Affiliation
Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany
Reinke, Simon;
Affiliation
Department of Genetics, University of Saarland (UdS), Saarbrücken, Germany
Walter, Jörn;
Affiliation
Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany
Mashreghi, Mir-Farzin;
Affiliation
Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany
Thurley, Kevin;
Affiliation
Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany
Radbruch, Andreas;
Affiliation
Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), Institute of the Leibniz Association, Berlin, Germany
Dong, Jun

Resident memory T lymphocytes (TRM) 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⁺ TRM are mobilized into the blood within 16 to 48 h after immunization in humans. This mobilization of TRM is cognate: TRM recognizing other antigens are not mobilized, unless they cross-react with the vaccine. We also demonstrate through methylome analyses that TRM 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, TRM of the Bm confer not only local, but also systemic immune memory.

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