Return to search

CD161+ Gamma Delta T-cells in health and liver disease

CD161 γδ T-cells have been implicated in the pathogenesis of Multiple Sclerosis however their role in health and chronic liver disease requires further exploration. In health, the majority of γδ T-cells expressed CD161 – a C-type lectin, and predominantly expressed the Vδ2 chain. The CD161+ γδ T-cells demonstrated a Th1-like pattern, expressing IFN-γ, TNF-α and Granzymes/Perforin when compared to the CD161- subset. The CD161+ γδ T-cells also expressed CCR6 and IL-18R thus also displaying a Th17-like pattern. These cells were also found in the lamina propria in the gut and rapidly expanded in the 1<sup>st</sup> few weeks of life in the periphery. On gene array analysis, there were 409 genes expressed on the CD161+ γδ T-cells when compared to their CD161-ve counterparts including those coding for β2 receptors, CCL20, Acetycholinesterase, CCR1 and IL-18R. A potential clinical correlation to cardiac diseases was found when the upregulated genes were analysed. When the CD161+ γδ and CD161+ αβ T-cell populations were compared via gene-array, an association with a risk variant for coeliac disease was found. Thus in health, CD161+ γδ T-cells are not only a distinct subset of T-cells (confirmed by a FACS approach and gene array methods), but also the expression of CD161 may be linked to common genetic signals downstream in cell processes and disease pathogenesis, irrespective of T-cell subset population. In chronic liver disease there was a significant reduction in the periphery of CD161+ γδ T-cells in patients with chronic Hepatitis C (HCV) and an increase in patients with Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis when compared with healthy individuals. The CD161+ γδ T-cells appeared to be of a different phenotype in HCV infection. There was no overall significant localisation into of CD161+ γδ T-cells patients with chronic liver disease or specifically in HCV infection. There was however a CD161+ γδ T-cell enrichment in the liver in patients with Non-Alcoholic Fatty Liver disease. The CD161+ γδ T-cells were also found in Hepatocellular Carcinoma tissue. Overall it appears the CD161+ γδ T-cells are indeed a unique subset, playing a distinct role in health, as part of an early innate response, but also potentially involved in disease pathogenesis.

Identiferoai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:604466
Date January 2013
CreatorsRajoriya, Neil
ContributorsKlenerman, Paul
PublisherUniversity of Oxford
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Sourcehttp://ora.ox.ac.uk/objects/uuid:fd3fb46a-bd46-4096-8f9f-0f8d092682dd

Page generated in 0.0024 seconds