Is it time to rethink the MS immune cell theory?

[MSUK]

Rituximab Efficiently Depletes Increased CD20-Expressing T Cells in Multiple Sclerosis Patients.

Palanichamy A, Jahn S, Nickles D, Derstine M, Abounasr A, Hauser SL, Baranzini SE, Leppert D, von Büdingen HC.

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+CD20dim T cells.

We show that in MS patients, increased levels of CD3+CD20dim 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.

Sources: J Immunol. 2014 Jun 13. pii: 1400118. [Epub ahead of print] & Pubmed PMID: 24928997 (16/06/14)