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Features of Human CD3+CD20+ T Cells

Elisabeth Schuh, Kerstin Berer, Matthias Mulazzani, Katharina Feil, Ingrid Meinl, Harald Lahm, Markus Krane, Rüdiger Lange, Kristina Pfannes, Marion Subklewe, Robert Gürkov, Monika Bradl, Reinhard Hohlfeld, Tania Kümpfel, Edgar Meinl and Markus Krumbholz
J Immunol July 13, 2016, 1600089; DOI: https://doi.org/10.4049/jimmunol.1600089
Elisabeth Schuh
*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;
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Kerstin Berer
‡Max-Planck Institute of Biochemistry, 82152 Martinsried, Germany;
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Matthias Mulazzani
§Department of Neurology, University Hospital, Ludwig Maximilian University, 81377 Munich, Germany;
¶Medical Graduate Center, Technical University, 81675 Munich, Germany;
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Katharina Feil
§Department of Neurology, University Hospital, Ludwig Maximilian University, 81377 Munich, Germany;
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Ingrid Meinl
*Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig Maximilian University, 82152 Martinsried, Germany;
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Harald Lahm
‖German Heart Center, Department of Cardiovascular Surgery and Experimental Surgery Laboratory, 80636 Munich, Germany;
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Markus Krane
‖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;
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Rüdiger Lange
‖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;
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Kristina Pfannes
**Department of Medicine III, University Hospital, Ludwig Maximilian University, 81377 Munich, Germany;
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Marion Subklewe
**Department of Medicine III, University Hospital, Ludwig Maximilian University, 81377 Munich, Germany;
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Robert Gürkov
††Department of Otolaryngology, University Hospital, Ludwig Maximilian University, 81377 Munich, Germany; and
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Monika Bradl
†Department of Neuroimmunology, Center for Brain Research, Medical University, 1090 Vienna, Austria;
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Reinhard Hohlfeld
*Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig Maximilian University, 82152 Martinsried, Germany;
‡‡Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany
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Tania Kümpfel
*Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig Maximilian University, 82152 Martinsried, Germany;
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Edgar Meinl
*Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig Maximilian University, 82152 Martinsried, Germany;
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Markus Krumbholz
*Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig Maximilian University, 82152 Martinsried, Germany;
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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.

Footnotes

  • This work was supported partially by Deutsche Forschungsgemeinschaft (Grant SFB TR128), the Munich Cluster for Systems Neurology (Grant ExC 1010 SyNergy), the Clinical Competence Network for Multiple Sclerosis, and Verein zur Therapieforschung für Multiple Sklerose-Kranke.

  • The online version of this article contains supplemental material.

  • Received January 15, 2016.
  • Accepted June 2, 2016.
  • Copyright © 2016 by The American Association of Immunologists, Inc.
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The Journal of Immunology: 208 (11)
The Journal of Immunology
Vol. 208, Issue 11
1 Jun 2022
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Features of Human CD3+CD20+ T Cells
Elisabeth Schuh, Kerstin Berer, Matthias Mulazzani, Katharina Feil, Ingrid Meinl, Harald Lahm, Markus Krane, Rüdiger Lange, Kristina Pfannes, Marion Subklewe, Robert Gürkov, Monika Bradl, Reinhard Hohlfeld, Tania Kümpfel, Edgar Meinl, Markus Krumbholz
The Journal of Immunology July 13, 2016, 1600089; DOI: 10.4049/jimmunol.1600089

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Features of Human CD3+CD20+ T Cells
Elisabeth Schuh, Kerstin Berer, Matthias Mulazzani, Katharina Feil, Ingrid Meinl, Harald Lahm, Markus Krane, Rüdiger Lange, Kristina Pfannes, Marion Subklewe, Robert Gürkov, Monika Bradl, Reinhard Hohlfeld, Tania Kümpfel, Edgar Meinl, Markus Krumbholz
The Journal of Immunology July 13, 2016, 1600089; DOI: 10.4049/jimmunol.1600089
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