Poster Presentation First Malaria World Congress 2018

Requirements for the formation of liver-resident memory T cells and their role in protection from malaria. (#299)

Lauren E Holz 1 2 , Vanessa Mollard 3 , Anton Cozijnsen 3 , Gayle M Davey 1 , Irina Caminschi 4 , Geoffrey I McFadden 3 , Daniel Fernandez-Ruiz 1 , William R Heath 1 2
  1. The Peter Doherty Institute, Melbourne, VIC, Australia
  2. The ARC Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, VIC, Australia
  3. School of BioSciences, University of Melbourne, Parkville, VIC, Australia
  4. Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia

We recently identified a population of tissue-resident memory T cells that migrate throughout the liver sinusoids, scanning hepatocytes to protect against malaria sporozoite challenge. To gain understanding of liver Trm cell development, we examined a number of different conditions for formation of this memory T cell subset. Endogenous liver Trm cells were found in naïve specific pathogen free mice, and their formation depended on antigenic stimulation and IL-15. Adoptive transfer of in vitro activated CD8+ T cells resulted in the formation of stable populations of liver Trm cells, indicating that antigenic stimulation within the liver was not essential for these cells to form. Liver Trm generated through a prime and trap vaccination approach or via transfer of in vitro activated T cells, patrolled the liver sinusoids and were required to express CXCR6 in order to be retained in the liver. Upon exposure to Plasmodium parasites (malaria), clusters of Trm and Tem could be found surrounding infected hepatocytes. Re-activated liver Trm expressed a variety of effector molecules including IFN-g, TNF-a and Granzyme B, and Trm were crucial for protection. Mice lacking CD4 T cells displayed a reduced capacity to clear parasites from the liver suggesting suboptimal Trm responses. Combined these data reveal a critical role for IL-15, CXCR6 and CD4 help in generating a stable liver Trm population capable of eliciting anti-parasite immunity.