title: Rituximab efficiently depletes increased CD20-expressing T cells in multiple sclerosis patients.
abstract: In multiple sclerosis (MS), B cell-depleting therapy using monoclonal anti-CD20 Abs, including rituximab (RTX) and ocrelizumab, effectively reduces disease activity. Based on indirect evidence, it is generally believed that elimination of the Ag-presenting capabilities and Ag nonspecific immune functions of B cells underlie the therapeutic efficacy. However, a small subset of T lymphocytes (T cells) was shown to also express CD20, but controversy prevails surrounding the true existence of this T cell subpopulation. Using single-cell imaging flow cytometry and expression profiling of sorted lymphocyte subsets, we unequivocally demonstrate the existence of CD3(+)CD20(dim) T cells. We show that in MS patients, increased levels of CD3(+)CD20(dim) T cells are effectively depleted by RTX. The pathological relevance of this T cell subset in MS remains to be determined. However, given their potential proinflammatory functionality, depletion of CD20-expressing T cells may also contribute to the therapeutic effect of RTX and other mAbs targeting CD20.
authors.affiliation: University of California, San Francisco, Department of Neurology, San Francisco, CA, USA.
authors.forename: Arumugam
authors.initials: A
authors.lastname: Palanichamy
authors.affiliation: University of California, San Francisco, Department of Neurology, San Francisco, CA, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Jahn
authors.affiliation: University of California, San Francisco, Department of Neurology, San Francisco, CA, USA.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Nickles
authors.affiliation: University of California, San Francisco, Department of Neurology, San Francisco, CA, USA.
authors.forename: Mia
authors.initials: M
authors.lastname: Derstine
authors.affiliation: University of California, San Francisco, Department of Neurology, San Francisco, CA, USA.
authors.forename: Aya
authors.initials: A
authors.lastname: Abounasr
authors.affiliation: University of California, San Francisco, Department of Neurology, San Francisco, CA, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hauser
authors.affiliation: University of California, San Francisco, Department of Neurology, San Francisco, CA, USA.
authors.forename: Sergio E
authors.initials: SE
authors.lastname: Baranzini
authors.affiliation: Department of Neurology, University Hospital, Basel, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Leppert
authors.affiliation: University of California, San Francisco, Department of Neurology, San Francisco, CA, USA.
authors.forename: H-Christian
authors.initials: HC
authors.lastname: von Büdingen
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018951:Antigens, CD20 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D000069283:Rituximab; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018941:Antigens, CD19; D018951:Antigens, CD20; D017252:CD3 Complex; D000069283:Rituximab