title: Features of Human CD3+CD20+ T Cells.
abstract: Monoclonal Abs against CD20 reduce the number of relapses in multiple sclerosis (MS); commonly this effect is solely attributed to depletion of B cells. Recently, however, a subset of CD3(+)CD20(+) T cells has been described that is also targeted by the anti-CD20 mAb rituximab. Because the existence of cells coexpressing CD3 and CD20 is controversial and features of this subpopulation are poorly understood, we studied this issue in detail. In this study, we confirm that 3-5% of circulating human T cells display CD20 on their surface and transcribe both CD3 and CD20. We report that these CD3(+)CD20(+) T cells pervade thymus, bone marrow, and secondary lymphatic organs. They are found in the cerebrospinal fluid even in the absence of inflammation; in the cerebrospinal fluid of MS patients they occur at a frequency similar to B cells. Phenotypically, these T cells are enriched in CD8(+) and CD45RO(+) memory cells and in CCR7(-) cells. Functionally, they show a higher frequency of IL-4-, IL-17-, IFN-γ-, and TNF-α-producing cells compared with T cells lacking CD20. CD20-expressing T cells respond variably to immunomodulatory treatments given to MS patients: they are reduced by fingolimod, alemtuzumab, and dimethyl fumarate, whereas natalizumab disproportionally increases them in the blood. After depletion by rituximab, they show earlier and higher repopulation than CD20(+) B cells. Taken together, human CD3(+)CD20(+) T cells pervade lymphatic organs and the cerebrospinal fluid, have a strong ability to produce different cytokines, and respond to MS disease modifying drugs.
authors.affiliation: Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig Maximilian University, 82152 Martinsried, Germany; Department of Neuroimmunology, Center for Brain Research, Medical University, 1090 Vienna, Austria;
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schuh
authors.affiliation: Max-Planck Institute of Biochemistry, 82152 Martinsried, Germany;
authors.forename: Kerstin
authors.initials: K
authors.lastname: Berer
authors.affiliation: Department of Neurology, University Hospital, Ludwig Maximilian University, 81377 Munich, Germany; Medical Graduate Center, Technical University, 81675 Munich, Germany;
authors.forename: Matthias
authors.identifier: 0000-0002-3517-5084
authors.initials: M
authors.lastname: Mulazzani
authors.affiliation: Department of Neurology, University Hospital, Ludwig Maximilian University, 81377 Munich, Germany;
authors.forename: Katharina
authors.initials: K
authors.lastname: Feil
authors.affiliation: Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig Maximilian University, 82152 Martinsried, Germany;
authors.forename: Ingrid
authors.initials: I
authors.lastname: Meinl
authors.affiliation: German Heart Center, Department of Cardiovascular Surgery and Experimental Surgery Laboratory, 80636 Munich, Germany;
authors.forename: Harald
authors.identifier: 0000-0002-4477-3406
authors.initials: H
authors.lastname: Lahm
authors.affiliation: German Heart Center, Department of Cardiovascular Surgery and Experimental Surgery Laboratory, 80636 Munich, Germany; German Center for Cardiovascular Research (partner site Munich Heart Alliance), 80636 Munich, Germany;
authors.forename: Markus
authors.initials: M
authors.lastname: Krane
authors.affiliation: German Heart Center, Department of Cardiovascular Surgery and Experimental Surgery Laboratory, 80636 Munich, Germany; German Center for Cardiovascular Research (partner site Munich Heart Alliance), 80636 Munich, Germany;
authors.forename: Rüdiger
authors.identifier: 0000-0002-6662-5957
authors.initials: R
authors.lastname: Lange
authors.affiliation: Department of Medicine III, University Hospital, Ludwig Maximilian University, 81377 Munich, Germany;
authors.forename: Kristina
authors.initials: K
authors.lastname: Pfannes
authors.affiliation: Department of Medicine III, University Hospital, Ludwig Maximilian University, 81377 Munich, Germany;
authors.forename: Marion
authors.initials: M
authors.lastname: Subklewe
authors.affiliation: Department of Otolaryngology, University Hospital, Ludwig Maximilian University, 81377 Munich, Germany; and.
authors.forename: Robert
authors.initials: R
authors.lastname: Gürkov
authors.affiliation: Department of Neuroimmunology, Center for Brain Research, Medical University, 1090 Vienna, Austria;
authors.forename: Monika
authors.identifier: 0000-0003-2239-1586
authors.initials: M
authors.lastname: Bradl
authors.affiliation: Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig Maximilian University, 82152 Martinsried, Germany; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hohlfeld
authors.affiliation: Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig Maximilian University, 82152 Martinsried, Germany;
authors.forename: Tania
authors.initials: T
authors.lastname: Kümpfel
authors.affiliation: Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig Maximilian University, 82152 Martinsried, Germany; edgar.meinl@med.uni-muenchen.de.
authors.forename: Edgar
authors.initials: E
authors.lastname: Meinl
authors.affiliation: Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig Maximilian University, 82152 Martinsried, Germany;
authors.forename: Markus
authors.initials: M
authors.lastname: Krumbholz
mesh_terms: D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D018951:Antigens, CD20 / Q000096:biosynthesis*; D017252:CD3 Complex / Q000096:biosynthesis*; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis; D000069462:Dimethyl Fumarate / Q000494:pharmacology; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D000069442:Natalizumab / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20; D017252:CD3 Complex; D016207:Cytokines; D007155:Immunologic Factors; D000069442:Natalizumab; D000074323:Alemtuzumab; D000069462:Dimethyl Fumarate; D000068876:Fingolimod Hydrochloride