Rituximab efficiently depletes increased CD20-expressing T cells in multiple sclerosis patients

J Immunol. 2014 Jul 15;193(2):580-586. doi: 10.4049/jimmunol.1400118. Epub 2014 Jun 13.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antigens, CD19 / genetics
  • Antigens, CD19 / immunology
  • Antigens, CD19 / metabolism
  • Antigens, CD20 / genetics
  • Antigens, CD20 / immunology*
  • Antigens, CD20 / metabolism
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • CD3 Complex / genetics
  • CD3 Complex / immunology
  • CD3 Complex / metabolism
  • Female
  • Flow Cytometry
  • Humans
  • Immunophenotyping
  • Lymphocyte Depletion*
  • Male
  • Middle Aged
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Oligonucleotide Array Sequence Analysis
  • Rituximab
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Transcriptome / genetics
  • Transcriptome / immunology
  • Young Adult

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD19
  • Antigens, CD20
  • CD3 Complex
  • Rituximab