Vγ9Vδ2 T cells are a minor subset of T cells in human blood that 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. Vγ9Vδ2 T cells can be skewed towards distinct effector functions, in analogy to, and beyond, the emerging plasticity of CD4+ T cells. Depending on the microenvironment, Vγ9Vδ2 T cells can assume features reminiscent of Th1, Th2, Th17 and Treg cells as well as professional antigen presenting cells (APCs). The main focus of this PhD was to investigate the role of the follicular B helper T (Tfh) cell derived cytokine IL-21 in enhancing the ability of human Vγ9Vδ2 T cells in providing B cell help. In order to try to mimic the physiological conditions in the GC, an in vitro system of autologous Vγ9Vδ2 T cells and B cells from tonsils or blood, the microbial metabolite HMB-PP and IL-21 was used. HMB-PP induced up-regulation of IL-21 receptor on Vγ9Vδ2 T cells. In return, IL-21 played a co-stimulatory role in the expression of the B cell-attracting chemokine CXCL13, the CXCL13 receptor CXCR5, the co-stimulatory molecules inducible co-stimulator (ICOS), OX40 and CD70 by activated Vγ9Vδ2 T cells. IL-21 also enhanced the ability of activated Vγ9Vδ2 T cells to support antibody production by B cells. Furthermore, Vγ9Vδ2 T cells not only themselves became highly activated APC marker expressing cells but also modified activation and APC marker expression on B cells. Findings presented in this thesis provide evidence that IL-21 contributes to the acquisition of B cell helper functions by human Vγ9Vδ2 T cells. In secondary lymphoid tissues, the interaction between HMB-PP-responsive Vγ9Vδ2 T cells, IL-21-producing Tfh cells and B cells is likely to impact on the generation of high affinity, class-switched antibodies in microbial infections
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:567344 |
| Date | January 2012 |
| Creators | Bansal, Raj Rani |
| Publisher | Cardiff University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://orca.cf.ac.uk/36649/ |
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