Poster Presentation The Australasian Society for Immunology 2017 Annual Scientific Meeting

Liver tissue resident memory T cells are formed under various conditions (#253)

Lauren E Holz 1 2 , Wei Yi Ng 2 3 4 , Julia E Prier 2 , David Freestone 2 , Kieran English 5 6 , Darryl N Johnson 1 2 , Vanessa Mollard 7 , Anton Cozijnsen 7 , Gayle M Davey 2 , Dale I Godfrey 1 2 , Geoffrey I McFadden 7 , Patrick J Bertolino 5 6 , Laura K Mackay 2 , Irina Caminschi 3 4 , William R Heath 1 2 , Daniel Fernandez-Ruiz 2
  1. The ARC Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, VIC, Australia
  2. The Peter Doherty Institute, Melbourne, VIC, Australia
  3. The Ferrier Research Institute, Wellington, New Zealand
  4. Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia
  5. Liver Immunology Program, Centenary Institute, Newtown, NSW, Australia
  6. AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital and Faculty of Medicine, University of Sydney, Newtown, NSW, Australia
  7. School of BioSciences, University of Melbourne, Parkville, VIC, Australia

We recently identified a population of tissue-resident memory T cells in the liver of mice immunized with radiation attenuated sporozoites or a novel prime-and-trap vaccine. These cells migrate throughout the liver sinusoid, scanning hepatocytes for infection, and protect against malaria sporozoite challenge. To gain understanding of when liver Trm form, we examined a number of different conditions for the generation of this novel memory T cell subset. Here, we reveal that liver Trm formed spontaneously in naïve inbred mice and T cell receptor transgenic mice. They also formed after transfer of activated TCR transgenic T cells into wild-type hosts, suggesting their development is a normal component to any CD8 T cell response. This conclusion was supported by detection of liver Trm after infection with blood-stage malaria, which does not infect the liver. Vaccination with RAS, which does infect the liver, generated proportionally more liver Trm, suggesting active infection of the liver promotes their formation. Examination of the spontaneous formation of liver Trm in various gene-deficient mice indicated that several factors were not required for their development (IFNa, IFNg, Sting, IL-4, TNF), but that IL-15 was essential. Interestingly, however, examination of Trm survival after multiple seeding events showed that initial numbers were not affected by subsequent new waves. This result implied limited competition for the liver Trm niche.