Volume 13 Supplement 2

Kitasato Symposium 2011: Translational prospects for cytokines in 2011

Open Access

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

  • Manfred Kopf1,
  • Luigi Tortola1,
  • Iwana Schmitz1,
  • Anja Fröhlich1,
  • Ivo Sonderegger1,
  • Helga Pawelski1 and
  • Christoph Schneider1
Arthritis Research & Therapy201113(Suppl 2):O9

DOI: 10.1186/ar3413

Published: 16 September 2011

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 [37].

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].

Authors’ Affiliations

(1)
Institute of Integrative Biology, Molecular Biomedicine

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. 10.1038/nri2580.PubMed CentralView ArticlePubMedGoogle Scholar
  2. Spolski R, Leonard WJ: Interleukin-21: basic biology and implications for cancer and autoimmunity. Annual review of immunology. 2008, 26: 57-79. 10.1146/annurev.immunol.26.021607.090316.View ArticlePubMedGoogle Scholar
  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. 10.1002/eji.200637023.View ArticlePubMedGoogle Scholar
  4. Elsaesser H, Sauer K, Brooks DG: IL-21 is required to control chronic viral infection. Science. 2009, 324: 1569-1572. 10.1126/science.1174182.PubMed CentralView ArticlePubMedGoogle Scholar
  5. Fröhlich A: IL-21R on T cells is critical for sustained functionality and control of chronic viral infection. Science. 2009, 324: 1576-1580. 10.1126/science.1172815.View ArticlePubMedGoogle Scholar
  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. 10.1038/nature04790.PubMed CentralView ArticlePubMedGoogle Scholar
  7. Yi JS, Zajac AJ: A vital role for interleukin-21 in the control of a chronic viral infection. Science. 2009, 324: 1572-1576. 10.1126/science.1175194.PubMed CentralView ArticlePubMedGoogle Scholar
  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.View ArticlePubMedGoogle Scholar
  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. 10.1002/eji.200838511.View ArticlePubMedGoogle Scholar
  10. Fröhlich A: IL-21 receptor signaling is integral to the development of Th2 effector responses in vivo. Blood. 2007, 109: 2023-2031. 10.1182/blood-2006-05-021600.View ArticlePubMedGoogle Scholar
  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.Google Scholar
  12. Tortola L: IL-21 induces death of marginal zone B cells during chronic inflammation. Blood. 2010, 116: 5200-5207. 10.1182/blood-2010-05-284547.View ArticlePubMedGoogle Scholar

Copyright

© BioMed Central Ltd 2011

Advertisement