You can manage bookmarks using lists, please log in to your user account for this.
Media type:
E-Article
Title:
Depletion of functionally active CD20+ T cells by rituximab treatment
Contributor:
Wilk, Esther;
Witte, Torsten;
Marquardt, Nicole;
Horvath, Tibor;
Kalippke, Katy;
Scholz, Kirsten;
Wilke, Nadine;
Schmidt, Reinhold E.;
Jacobs, Roland
imprint:
Wiley, 2009
Published in:Arthritis & Rheumatism
Language:
English
DOI:
10.1002/art.24998
ISSN:
0004-3591;
1529-0131
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Rituximab is a therapeutic anti‐CD20 antibody used for in vivo depletion of B cells in proliferative and autoimmune diseases. However, the mechanisms of action are not fully understood, since not all of the therapy‐mediated effects can be explained by the depletion of antibody‐secreting cells. In addition to B cells, there is also a small population of T cells coexpressing CD20 in all individuals. This study was conducted to examine the phenotype and function of CD3+CD20+ T cells in patients with rheumatoid arthritis (RA) and healthy controls.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The phenotype and apoptosis of peripheral blood mononuclear cells from healthy donors and RA patients were examined by 4‐color fluorescence‐activated cell sorting analyses. Cytokine production was determined by intracellular staining and measurement of cytokines in the supernatants. Proliferation of sorted T cell populations was analyzed using <jats:sup>3</jats:sup>H‐thymidine uptake assays.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In healthy individuals, 0.1–6.8% of peripheral blood T cells (mean 1.6%; n = 142) coexpressed CD20, which was not significantly different from that in the peripheral blood of RA patients, in whom 0.4–2.6% of T cells (mean 1.2%; n = 27) were CD20+. During rituximab therapy, the CD20+ T cells along with the B cells were eliminated from the RA peripheral blood. Among the CD20+ T cells, 45% coexpressed CD8 and 55% coexpressed CD4. Polyclonal CD3+CD20+ cells were functionally characterized by constitutive cytokine production (i.e., interleukin‐1β and tumor necrosis factor α), a low proliferative capacity, a high activation state, and enhanced susceptibility to apoptosis.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>These findings suggest that CD20+ T cells represent a terminally differentiated cell type with immune‐regulatory and proinflammatory capacities. Depletion of CD20+ T cells may be an additional mechanism by which anti‐CD20 therapy functions in patients with RA.</jats:p></jats:sec>