Science Bite (3 minute oral presentation with PPT in live session with pre-recorded e-poster) Lorne Infection and Immunity 2021

Liver resident CD4 T cell in malaria infection (#104)

Matthias H Enders 1 2 3 , Lynette Beattie 1 2 , Anton Cozsijinsen 4 , Irina Caminschi 5 , Geoffrey I McFadden 4 , Elvira Mass 3 , Daniel Fernandez Ruiz 1 , William R Heath 1 2
  1. Department of Microbiology and immunology, University of Melbourne, Melbourne, Victoria, Australia
  2. The ARC Centre of Excellence in Advanced Molecular Imaging University of Melbourne, Parkville, Victoria , Australia
  3. Limes-Institute, University of Bonn, Bonn, Germany
  4. School of BioSciences, University of Melbourne, Melbourne, VIC, Australia
  5. Infection and Immunity Program & Department of Biochemistry and Molecular BiologyClayton, Monash University , Clayton, Victoria, Australia

Malaria is caused by different Plasmodium species that can infect a variety of animals including humans and rodents. The life cycle of these parasites is complex, including a liver-stage followed by a blood-stage in their vertebrate hosts. While the host’s immune response against each of these stages is incompletely understood, CD4 T cells are known to play an important role in immunity to Plasmodium infection during both stages. This project aims to examine the specific CD4 T cell response to a novel MHC II-restricted epitope in Plasmodium in C57BL/6 mice and to characterize the protective capacity of these T cells. Given the importance of tissue-resident memory T cells (Trm cells) in peripheral immunity, we focused our study on the formation of CD4 Trm cells in the liver and protection against liver-stage parasites. To do this, we made use of a recently generated TCR transgenic mouse line, termed PbT-II, that responds to an epitope, abbreviated as YYI, expressed by both rodent and human Plasmodium parasites. Different priming methods were used to induce PbT-II priming; these included injection of anti-Clec9A antibody attached to the YYI epitope (Clec9A-YYI) or infection with radiation attenuated Plasmodium sporozoites (RAS), which infect the liver but do not progress to the blood.

To test whether PbT-II T cells formed tissue-resident memory T cells, GFP-expressing PbT-II transgenic T cells were injected into naïve B6 mice that were then primed with Clec9A-YYI or RAS. Flow cytometric analyses 35 days later revealed the existence of a memory PbT-II cell population in the liver expressing surface markers associated with tissue-residency. Parabiosis surgery on RAS vaccinated mice confirmed the residency of this PbT-II cell population in the liver. Gene expression analysis of these CD4 T cells further revealed a similar expression profile to that of CD8 liver resident T cells. Our results indicate that CD4 Trm cells form in the liver during malaria infection and share gene expression profiles with CD8 liver Trm cells. Our ongoing studies will determine whether CD4 T cell lineage-specific differences affect formation of liver Trm cells and their role in protection from infection.