The immunobiology of human hepatic gamma delta T cells

Hunter, Stuart (2018). The immunobiology of human hepatic gamma delta T cells. University of Birmingham. Ph.D.

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Abstract

The liver contains a number of tissue-associated lymphocyte populations, of which many have been implicated in the pathogenesis of chronic liver diseases. \(\gamma\delta\) T cells, particularly the \(V\delta2^{neg}\) 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 \(\gamma\delta\) T cells was explored with an emphasis on highlighting any potential role in chronic liver disease and also to further understanding of tissue-associated \(\gamma\delta\) T cells, using the liver as a model tissue. Intrahepatic \(\gamma\delta\) T cells were predominantly localised in the sinusoids and did not increase in frequency with chronic inflammation. \(V\delta2^{neg}\) cells exhibited private TCR clonal focussing, with complex CDR3 regions suggestive of antigen-driven expansions, concordant with a loss of naive-like \(CD27^{hi}\) cells present in the periphery. Expanded clonotypes were phenotypically \(T_{EM}\)- or \(T_{EMRA}\)-like, with \(T_{EMRA}\)-like clonotypes shared between liver and blood and resembling vasculature-associated virus-specific \(CD8^+\) T cells while \(T_{EM}\) clonotypes were identified only in the liver and resembled tissue-resident \(CD8^+\) T cells. These findings suggest that disease has minimal impact on intrahepatic \(\gamma\delta\) T cells, while supporting an adaptive paradigm for these cells in the formation of tissue-associated subsets.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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