Cendón and Wu et al. re-immunized eleven 28-43 y.o. healthy volunteers with the measles, mumps, and rubella (MMR) vaccine. As early as 16h, MMR-specific CD4+ T cells (CD40L+cytokine+ with ex vivo restimulation) increased in the blood and remained detectable 14 days later. Resident memory-phenotype T cells (i.e. CD40L+cytokine+ without restimulation) were detected and, while initially non-proliferative, expressed Ki67 over time. Vaccination expanded cross-reactive T cells and diversified MMR-specific TCR clonotypes in blood. Epigenetic methylome analysis suggested the newly mobilized T cell clones originated in the bone marrow.
Contributed by Alex Najibi
ABSTRACT: 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.
Author Info: (1) Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany. (2) Cell Biology, Deutsches Rheuma-Forschungszentrum B
Author Info: (1) Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany. (2) Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany. (3) Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany. (4) Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany. (5) Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany. (6) Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, USA. (7) Otto-Warburg-Laboratory, Computational Epigenomics, Max Planck Institute for Molecular Genetics, Berlin, 14195, Germany. (8) Department of Genetics, University of Saarland (UdS), Campus, Saarbrücken, 66123, Germany. (9) Department of Genetics, University of Saarland (UdS), Campus, Saarbrücken, 66123, Germany. (10) Department of Genetics, University of Saarland (UdS), Campus, Saarbrücken, 66123, Germany. (11) Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany. (12) Mass Cytometry, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany. (13) Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany. (14) Therapeutic Gene Regulation, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany. (15) Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany. (16) Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany. (17) Department of Chemical and Product Safety, German Federal Institute for Risk Assessment, Berlin, Germany. (18) Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany. (19) Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany. Schwiete-Laboratory for Microbiota and Inflammation, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany. (20) Institute for Medical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany. BIH Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Berlin, Germany. (21) Innate Immunity, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany. Medical Department / Gastroenterology, Infectiology and Rheumatology, Charité - Universitätsmedizin Berlin, Berlin, Germany. (22) Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Bejing, China. University of Chinese Academy of Sciences, Bejing, China. Zhengzhou University, Zhengzhou, China. (23) Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany. (24) Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany. (25) BIH Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Berlin, Germany. (26) Department of Genetics, University of Saarland (UdS), Campus, Saarbrücken, 66123, Germany. (27) Therapeutic Gene Regulation, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany. BIH Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, Berlin, Germany. (28) Systems Biology of Inflammation, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany. Institute for Theoretical Biology, Humboldt University Berlin, Germany. (29) Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany. (30) Cell Biology, Deutsches Rheuma-Forschungszentrum Berlin (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
