The liver contains a number of tissue-associated lymphocyte populations, of which many have been implicated in the pathogenesis of chronic liver diseases. γδ T cells, particularly the Vδ2<sup>neg</sup> subset, are known to comprise a substantial proportion of tissue-associated lymphocytes, although their immunobiology remains poorly understood. Here, the localisation, TCR diversity, immunophenotype and function of human intrahepatic γδ T cells was explored with an emphasis on highlighting any potential role in chronic liver disease and also to further understanding of tissue-associated γδ T cells, using the liver as a model tissue. Intrahepatic γδ T cells were predominantly localised in the sinusoids and did not increase in frequency with chronic inflammation. Vδ2<sup>neg</sup> cells exhibited private TCR clonal focussing, with complex CDR3 regions suggestive of antigen-driven expansions, concordant with a loss of naive-like CD27<sup>hi</sup> cells present in the periphery. Expanded clonotypes were phenotypically T<sub>EM</sub>- or T<sub>EMRA</sub>-like, with T<sub>EMRA</sub>-like clonotypes shared between liver and blood and resembling vasculature-associated virus-specific CD8⁺ T cells while T<sub>EM</sub> clonotypes were identified only in the liver and resembled tissue-resident CD8⁺ T cells. These findings suggest that disease has minimal impact on intrahepatic γδ T cells, while supporting an adaptive paradigm for these cells in the formation of tissue-associated subsets.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:753083 |
| Date | January 2018 |
| Creators | Hunter, Stuart |
| Publisher | University of Birmingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://etheses.bham.ac.uk//id/eprint/8340/ |
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