Innate T cells are significantly altered in the livers of patients with alcoholic liver disease — ASN Events
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Innate T cells are significantly altered in the livers of patients with alcoholic liver disease (#181)

Yasmeen G Ghnewa 1 , Shirin E Khorsandi 2 , Xiaohong Huang 1 , Laura Ramsay 2 , Wayel Jassem 1 , Nigel Heaton 2 , Yun Ma 1
  1. Liver studies, King's College Hospital, King's College London, London, UK
  2. Liver studies, , King's College Hospital, London, UK

Innate T cells include natural killer T (NKT) cells, mucosa-associated invariant T (MAIT) cells, and gamma delta (γδ) T cells. Innate T cells are enriched in the human liver, with MAIT cells making up to 50% of hepatic T cells. It's been reported recently that the frequencies of innate T cells was reduced in the liver of mixed chronic liver disease cohort compared to healthy controls (HC). However, little is known about the affects of alcoholic liver disease (ALD) on liver-resident human innate T cells. We aimed to characterize these cells in the liver of patients with ALD.  

Intrahepatic mononuclear cells (HMC) from liver perfusates of 10 explanted ALD livers and 10 healthy controls (HC) were analysed by flow cytometry for the expression of CD3, Vα24-Jα18, Vα7.2, CD161, γδ-TCR, CD19, CD4, CD8, CD40, MHC-II, and CD1d.

The frequency of T cells within HMC was significantly reduced in patients with ALD compared to HC (P=0.0036). The frequencies of MAIT cells and γδ T cells as a proportion of total T cells were significantly reduced (P=0.004) and (P=0.01) respectively. The proportions of total T cell subsets based on CD4 and CD8 expression were significantly skewed in patients with ALD. CD4+ T cells were significantly increased (P=0.0001), while CD8+ T cells (P=0.01) and CD4-CD8- T cells (P=0.0003) were significantly reduced. B cells and monocytes from ALD patients showed a significant up regulation of CD40 and  CD1d, but not MHC class II compared to HC.

MAIT cells and γδ T cells are reduced in frequency in the liver of patients with ALD. The selective up regulation of CD1d and CD40 may be relevant to the cause of depletion in the innate T cell pool . These findings warrant further investigation into the role of MAIT and γδ T cells in the pathogenesis of ALD.