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Anti-CD20 antibody is an efficient therapeutic tool for the selective removal of autoreactive T cells

Nature Clinical Practice Rheumatology volume 5, pages 80–82 (2009)Cite this article

Rituximab, a chimeric IgG1 monoclonal antibody that specifically binds to CD20 on B cells, has demonstrated surprising efficacy in the treatment of autoimmune diseases that are predominantly mediated by T helper (TH) cells, such as rheumatoid arthritis, multiple sclerosis (MS), lupus nephritis and idiopathic thrombocytopenic purpura,1,2,3,4,5 as well as in mouse models of autoimmune diabetes.6 These findings have led investigators to speculate that B cells might have a primary and initiating role in these autoimmune diseases. In this Viewpoint I argue, however, that the action of anti-CD20 therapy is in fact specific for autoreactive T cells.

The roles of B cells in the action of rituximab are generally thought to relate to autoantigen presentation, excessive costimulation, and inflammatory cytokine and chemokine production, which all lead to the attraction and expansion of autoreactive inflammatory T cells at the expense of regulatory T (TREG) cells. Other antigen presenting cells (APCs) such as dendritic cells (DCs) and macrophages, however, are activated and prevalent in lesions of TH-cell-mediated autoimmune diseases. These cells are also quite capable of carrying out the pathogenic functions usually attributed to B cells. Autoreactive B cells could be the most efficient APC for autoreactive T cells previously primed by autoantigen, which would be an important factor in explaining the efficacy of rituximab in TH-cell-mediated autoimmune diseases if the amount of autoantigen was limited; however, this is not the case in these autoimmune diseases, where the entire target organ—such as the brain in multiple sclerosis or all the nucleated cells undergoing apoptosis in the case of lupus—provides abundant supply of autoantigens. Moreover, B cells might go on to produce proinflammatory cytokines to induce expansion of TH17 cells, but autoreactive TH1 cells are the initiators of autoimmunity in all of the above mentioned diseases, as well as in murine lupus,5 and also have a major role in disease pathogenesis. B cells cannot, however, present autoantigens to induce TH1 cell differentiation because they do not produce interleukin 12.

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Acknowledgements

This work was supported by NIH grants R37–AR39157 and RO1–AI41985.

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  1. Division of Rheumatology, Northwestern University, Feinberg School of Medicine, 240 East Huron Street, McGaw #M300, Chicago, IL 60611, USA skd257@northwestern.edu

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  1. SK Datta is a Professor in the Departments of Medicine and Microbiology-Immunology at Northwestern University Feinberg School of Medicine, Chicago, IL, USA.,

    Syamal K Datta

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Datta, S. Anti-CD20 antibody is an efficient therapeutic tool for the selective removal of autoreactive T cells. Nat Rev Rheumatol 5, 80–82 (2009). https://doi.org/10.1038/ncprheum0983

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