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: Arumugam Palanichamy, Sarah Jahn, Dorothee Nickles, Mia Derstine, Aya Abounasr, Stephen L Hauser, Sergio E Baranzini, David Leppert, H-Christian von Büdingen
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 193 Issue 2 Pg. 580-586 (Jul 15 2014) ISSN: 1550-6606 [Electronic] United States
• PMID: 24928997 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 by The American Association of Immunologists, Inc.

Chemical References

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

Topics

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