IL-21 enhances the potential of human γδ T cells to provide B-cell help.
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.
Department of Infection, Immunity and Biochemistry, School of Medicine, Cardiff University, Cardiff, United Kingdom.
Raj R
RR
Bansal
Charles R
CR
Mackay
Bernhard
B
Moser
Matthias
M
Eberl
D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D054382:Chemokine CXCL13 / Q000276:immunology; D011756:Diphosphates / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000276:immunology; D007378:Interleukins / Q000276:immunology* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D054380:Receptors, CXCR5 / Q000276:immunology; D015854:Up-Regulation; D000098546:Interleukin-21
C443995:4-hydroxy-3-methylbut-2-enyl pyrophosphate; C110663:CXCL13 protein, human; C095085:CXCR5 protein, human; D054382:Chemokine CXCL13; D011756:Diphosphates; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D007378:Interleukins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054380:Receptors, CXCR5; D000098546:Interleukin-21