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

Research output: Contribution to journalArticlepeer-review

132 Scopus citations

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 CCR72- 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.

Original languageEnglish
Pages (from-to)1111-1117
Number of pages7
JournalJournal of Immunology
Volume197
Issue number4
DOIs
StatePublished - 15 Aug 2016

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