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

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

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Author affiliations

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

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Citation and License

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: http://arthritis-research.com/content/13/S2/O9


Published:16 September 2011

© 2011 Kopf et al.

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].

References

  1. Rochman Y, Spolski R, Leonard WJ: New insights into the regulation of T cells by gamma(c) family cytokines.

    Nat Rev Immunol 2009, 9:480-490. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  2. Spolski R, Leonard WJ: Interleukin-21: basic biology and implications for cancer and autoimmunity.

    Annual review of immunology 2008, 26:57-79. PubMed Abstract | Publisher Full Text OpenURL

  3. Bachmann MF, Wolint P, Walton S, Schwarz K, Oxenius A: Differential role of IL-2R signaling for CD8+ T cell responses in acute and chronic viral infections.

    European journal of immunology 2007, 37:1502-1512. PubMed Abstract | Publisher Full Text OpenURL

  4. Elsaesser H, Sauer K, Brooks DG: IL-21 is required to control chronic viral infection.

    Science 2009, 324:1569-1572. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  5. Fröhlich A, et al.: IL-21R on T cells is critical for sustained functionality and control of chronic viral infection.

    Science 2009, 324:1576-1580. PubMed Abstract | Publisher Full Text OpenURL

  6. Williams MA, Tyznik AJ, Bevan MJ: Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells.

    Nature 2006, 441:890-893. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  7. Yi JS, Zajac AJ: A vital role for interleukin-21 in the control of a chronic viral infection.

    Science 2009, 324:1572-1576. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  8. Coquet JM, Chakravarti S, Smyth MJ, Godfrey DI: Cutting edge: IL-21 is not essential for Th17 differentiation or experimental autoimmune encephalomyelitis.

    J Immunol 2008, 180:7097-7101. PubMed Abstract | Publisher Full Text OpenURL

  9. Sonderegger I, Kisielow J, Meier R, King C, Kopf M: IL-21 and IL-21R are not required for development of Th17 cells and autoimmunity in vivo.

    European journal of immunology 2008, 38:1833-1838. PubMed Abstract | Publisher Full Text OpenURL

  10. Fröhlich A, et al.: IL-21 receptor signaling is integral to the development of Th2 effector responses in vivo.

    Blood 2007, 109:2023-2031. PubMed Abstract | Publisher Full Text OpenURL

  11. Bessa J, Kopf M, Bachmann MF: Cutting Edge: IL-21 and TLR Signaling Regulate Germinal Center Responses in a B Cell-Intrinsic Manner.

    J Immunol 2010, 1-6. OpenURL

  12. Tortola L, et al.: IL-21 induces death of marginal zone B cells during chronic inflammation.

    Blood 2010, 116:5200-5207. PubMed Abstract | Publisher Full Text OpenURL