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

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 (T(FH) ) 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 T(FH) cells and B cells in secondary lymphoid tissues is likely to impact on the generation of high affinity, class-switched antibodies in microbial infections.

• Authors: Raj R Bansal, Charles R Mackay, Bernhard Moser, Matthias Eberl
• Journal: European journal of immunology (Eur J Immunol) Vol. 42 Issue 1 Pg. 110-9 (Jan 2012) ISSN: 1521-4141 [Electronic] Germany
• PMID: 22009762 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• 4-hydroxy-3-methylbut-2-enyl pyrophosphate
• CXCL13 protein, human
• CXCR5 protein, human
• Chemokine CXCL13
• Diphosphates
• ICOS protein, human
• Inducible T-Cell Co-Stimulator Protein
• Interleukins
• Receptors, Antigen, T-Cell, gamma-delta
• Receptors, CXCR5
• interleukin-21

Topics

• B-Lymphocytes (drug effects, immunology)
• Chemokine CXCL13 (immunology)
• Diphosphates (pharmacology)
• Flow Cytometry
• Humans
• Inducible T-Cell Co-Stimulator Protein (immunology)
• Interleukins (immunology, pharmacology)
• Leukocytes, Mononuclear (drug effects, immunology)
• Lymphocyte Activation (drug effects)
• Receptors, Antigen, T-Cell, gamma-delta (immunology)
• Receptors, CXCR5 (immunology)
• Up-Regulation