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This article is part of the supplement: Kitasato Symposium 2011: Translational prospects for cytokines in 2011

Open Badges Oral presentation

Orchestration of B and T cell responses in health and disease by common gamma chain family cytokines with a focus on IL-21

Manfred Kopf*, Luigi Tortola, Iwana Schmitz, Anja Fröhlich, Ivo Sonderegger, Helga Pawelski and Christoph Schneider

  • * Corresponding author: Manfred Kopf

Author Affiliations

Institute of Integrative Biology, Molecular Biomedicine, ETH Zürich, Switzerland

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Arthritis Research & Therapy 2011, 13(Suppl 2):O9  doi:10.1186/ar3413

The electronic version of this article is the complete one and can be found online at:

Published:16 September 2011

© 2011 Kopf et al.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Oral presentation

Members of a subfamily of the type 1 four-helix-bundle cytokines with receptors sharing the common gamma (cγ) chain including IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 have distinct activities on the differentiation of effector, memory, and regulatory T cells [1,2]. Furthermore, IL-2, IL-4, and IL-21 serve distinct roles in control of B cell development and differentiation to antibody producing cells. We and others recently reported that both IL-2 and IL-21 are essential for maintenance of CD8 T cells and control of chronic viral infection, while both cytokines are dispensable for expansion and contraction of CD8 T cells during acute and resolved viral infection [3-7].

While IL-21 has been implicated in cross-regulation of Th17 cells and inducible regulatory T cells (Treg) in vitro, development of Th17 and Treg cells and consequently organ-related autoimmune disease remain unaffected in IL-21R-deficient mice in vivo [8,9]. In contrast, we now found that IL-21 can potently inhibit proliferation and function of inducible and natural Treg cells in models of T cell transfer colitis, viral infection, and asthma. Increased numbers of Tregs in IL-21R-deficient mice offer an explanation for suppression of Th2-mediated asthma and susceptibility to chronic viral infection described in the knockout mice [5,10].

Furthermore, the importance of IL-21 for B cell and antibody responses has been well established. Recently, it has been suggested that IL-21 is crucial for development of T follicular helper cells (Tfh) and defective B cell responses in IL-21R-deficient mice are due to the absence of Tfh cells. However, we found that germinal center development and antibody responses were severely impaired in mice that lack IL-21R specifically on B cells suggesting that IL-21 regulates germinal center responses in a B cell intrinsic manner [11]. In addition, we have shown that requirement of IL-21 for a B cell response is overcome by immunization with particulate antigens containing TLR7/8 ligands (such as viral RNS). These data demonstrate that innate pathogen patterns (PAMPs) and Th cell derived signals co-operate in the induction of optimal IgG responses. Interestingly, in contrast to follicular B cell responses, IL-21 has been shown to negatively regulate marginal zone (MZ) B-cell survival and antibody production to Streptococous pneumonia [12].


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