Poster Presentation Lorne Infection and Immunity 2022

Inflammatory bowel disease remodels circulating and tissue-resident populations of human Vd1+ T cells. (#119)

Priyanka PC Chevour 1 , Anouk AvB von Borstel 1 , Edward EG Giles 2 , Jamie JR Rossjohn 1 3 , Martin MD Davey 1
  1. Infection and immunity program, Department of biochemistry and molecular biology, Monash University, Clayton, Victoria, Australia
  2. Department of Pediatrics, , Monash University and Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medicine, Clayton, Victoria, Australia
  3. Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom

γδ T cells have evolved as a third lymphocyte lineage alongside αβ T cells and B cells over millions of years of vertebrate evolution1. Human gd T cells constitute only a small proportion of all the circulating T lymphocytes in the blood but are enriched at mucosal barriers2. Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD) is thought to involve a dysregulated response from the mucosal immune system to the intestinal microbiota resulting in chronic inflammation of the gastrointestinal tract3. Here, we investigated the dynamics of human paediatric gd T cell subsets in the intestinal tissue and circulation at the early stages of IBD. Using immunophenotyping and T cell receptor (TCR) repertoire profiling we found that children at the first diagnosis of IBD displayed clonal populations of Vd1+ TCRs in the blood compared to age and gender matched healthy children. Moreover, circulating Vd1+ T cells in IBD children had shifted their phenotype from a CD27+ CD28+ naïve-like population to a cytotoxic CD27neg effector population. We then explored the relationship of circulating and intestinal resident populations of Vd1+ T cells. Firstly, we found that expanded Vd1+ T cell clonotypes in circulation, duodenum, terminal ileum and rectum contained unique tissue-location dependent TCR repertoires. Secondly, chronic Crohn’s disease associated inflammation drove the remodelling of terminal ileum resident Vd1+ T cells. Our study indicates that tissue-resident Vd1+ T cells in discrete niches of the intestine display unique TCR repertoires. Morevoer, the onset of IBD has a major impact on intestinal and circulating populations of Vd1+ T cells. These findings show that the γδ T cell repertoire is highly responsive to the early stages of chronic intestinal inflammation

  1. 1. Hirano, M., et al., Evolutionary implications of a third lymphocyte lineage in lampreys. Nature, 2013. 501(7467): p. 435-8
  2. 2. Deusch, K., et al., A major fraction of human intraepithelial lymphocytes simultaneously expresses the gamma/delta T cell receptor, the CD8 accessory molecule and preferentially uses the V delta 1 gene segment. Eur J Immunol, 1991. 21(4): p. 1053-9.
  3. 3. Larmonier, C.B., et al., T Lymphocyte Dynamics in Inflammatory Bowel Diseases: Role of the Microbiome. Biomed Res Int, 2015. 2015: p. 504638.