Year: 2018
Type: dissertation
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. \n \n
Author: Stuart Hunter
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2897681116