IL-21 inhibits T cell IL-2 production and impairs Treg homeostasis
- Attridge, Kesley Medical Research Council Centre for Immune Regulation, University of Birmingham Medical School, Birmingham, United Kingdom; and
- Wang, Chun Jing Medical Research Council Centre for Immune Regulation, University of Birmingham Medical School, Birmingham, United Kingdom; and
- Wardzinski, Lukasz Medical Research Council Centre for Immune Regulation, University of Birmingham Medical School, Birmingham, United Kingdom; and
- Kenefeck, Rupert Medical Research Council Centre for Immune Regulation, University of Birmingham Medical School, Birmingham, United Kingdom; and
- Chamberlain, Jayne L. Medical Research Council Centre for Immune Regulation, University of Birmingham Medical School, Birmingham, United Kingdom; and
- Manzotti, Claire Medical Research Council Centre for Immune Regulation, University of Birmingham Medical School, Birmingham, United Kingdom; and
- Kopf, Manfred Institute of Integrative Biology, Molecular Biomedicine, Eidgenössische Technische Hochschule Zürich, Schlieren, Switzerland
- Walker, Lucy S. K. Medical Research Council Centre for Immune Regulation, University of Birmingham Medical School, Birmingham, United Kingdom; and
Published in:
- Blood. - American Society of Hematology. - 2012, vol. 119, no. 20, p. 4656-4664
English
Abstract
Modulation of regulatory T cell (Treg) suppression has important implications for vaccine development, the effectiveness of tumor surveillance, and the emergence of autoimmunity. We have previously shown that the cytokine IL-21 can counteract Treg suppression. However, whether this reflects an effect of IL-21 on Treg, conventional T cells, or antigen-presenting cells is not known. Here we have used lymphocyte populations from IL-21R–deficient mice to pinpoint which cell type needs to be targeted by IL-21 for Treg suppression to be overcome. We show that IL-21 counteracts suppression by acting on conventional T cells and that this is associated with inhibition of IL-2 production. Despite the lack of IL-2, conventional T-cell responses proceed unimpaired because IL-21 can substitute for IL-2 as a T cell growth factor. However, IL-21 is unable to substitute for IL-2 in supporting the Treg compartment. Thus, IL-21 signaling in conventional T cells indirectly impacts Treg homeostasis by decreasing IL-2 availability. These data demonstrate that IL-21 and IL-2 can have overlapping roles in promoting conventional T-cell responses but play distinct roles in controlling Treg homeostasis and function. The data also suggest a new paradigm whereby cytokines can promote immunity by inhibiting IL-2.
- Language
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- English
- Open access status
- bronze
- Identifiers
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- DOI 10.1182/blood-2011-10-388546
- ISSN 0006-4971
- Persistent URL
- https://folia.unifr.ch/global/documents/267831
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