Oral Presentation ASDR-AWTRS-MEPSA 2018 Joint Meeting

Identification of a committed precursor to the tissue-resident memory T cell fate (#41)

Julia Prier 1 , Simone L Park 1 , Susan N Christo 1 , David Freestone 1 , Brooke Davies 1 , Svetoslav Chakarov 2 , Xiaomeng Zhang 2 , Gabrielle T Belz 3 , Jinmiao Chen 2 , Francis R Carbone 1 , Florent Ginhoux 2 , Laura K Mackay 1
  1. Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia
  2. Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore
  3. Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia

Tissue-resident memory T cells (TRM) persist in barrier tissues where they provide site-specific immune protection. However, the cell fate decisions and lineage pathways that lead to TRM commitment remains unclear. Here, using indexed single cell RNA-sequencing, we found that a distinct TRM precursor (pTRM) can be found in the secondary lymphoid organs early following infection. To characterize this population further, we developed a novel barcoding system where cellular division could be used as an unbiased proxy for cell fate, which allowed the permanent identification of T cells after infection based on the number of cell divisions experienced during T cell priming. Using this system, we show that pTRM undergo relatively fewer rounds of cellular division in the skin-draining lymph node after HSV infection, and these cells preferentially give rise to TRM in the tissue. Transcriptional profiling showed that a substantial number of TRM core signature genes are upregulated on pTRM early after T cell priming in the lymphoid organs. In all, we propose a two-wave differentiation pathway for TRM development. The first wave poises a precursor population at the site of priming and the second wave occurs within the tissue niche and commits the cell to the TRM fate. These findings provide a platform for manipulation of pTRM cells to enhance tissue-specific protection against infectious diseases and cancers or reduce autoimmune-related disease burden.