IL-21 enhances the potential of human γδ T cells to provide B-cell help

Authors

  • Raj R. Bansal,

    1. Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff University, Cardiff, United Kingdom
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  • Charles R. Mackay,

    1. Faculty of Medicine, Nursing and Health Services, Monash University, Clayton, Australia
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  • Bernhard Moser,

    1. Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff University, Cardiff, United Kingdom
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  • Matthias Eberl

    Corresponding author
    1. Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff University, Cardiff, United Kingdom
    • Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff University, Henry Wellcome Building, Heath Park, Cardiff CF14 4XN, United Kingdom Fax: +44-29-206-87303

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Abstract

Vγ9/Vδ2 T cells are a minor subset of T cells in human blood and differ from all other lymphocytes by their specific responsiveness to (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), a metabolite produced by a large range of microbial pathogens. Vγ9/Vδ2 T cells can be skewed towards distinct effector functions, in analogy to, and beyond, the emerging plasticity of CD4+ T cells. As such, depending on the microenvironment, Vγ9/Vδ2 T cells can assume features reminiscent of Th1, Th2, Th17 and Treg cells as well as professional APCs. We here demonstrate that Vγ9/Vδ2 T cells express markers associated with follicular B helper T (TFH) cells when stimulated with HMB-PP in the presence of IL-21. HMB-PP induces upregulation of IL-21R on Vγ9/Vδ2 T cells. In return, IL-21 plays a co-stimulatory role in the expression of the B-cell-attracting chemokine CXCL13, the CXCL13 receptor CXCR5 and the inducible co-stimulator by activated Vγ9/Vδ2 T cells, and enhances their potential to support antibody production by B cells. The interaction between HMB-PP-responsive Vγ9/Vδ2 T cells, IL-21-producing TFH cells and B cells in secondary lymphoid tissues is likely to impact on the generation of high affinity, class-switched antibodies in microbial infections.

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