Poster Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2024

T-bet high expressing CD4 T cell progenitors seed TRM cells in the peripheral tissues     (#135)

Amania A. Sheikh 1 2 , Tom Weber 1 2 , Hanna Abberger 1 2 , Carolina Alvarado 1 2 , Benjamin Broomfield 1 2 , Sara Tomei 1 2 , Shalin H. Naik 1 2 , Joanna R. Groom 1 2
  1. Division of Immunology, Walter Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  2. Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia

CD4+ tissue resident memory T cells (TRM) are the most abundant T cells in the memory pool that are permanently retained in peripheral tissues and have the ability to mount direct and rapid immune response against re-invading pathogens. However, cellular pathways underlying the formation and maintenance of TRM cells are unclear and is of significant therapeutic interest. Using an in vivo cellular barcoding strategy, we investigated the relatedness of T cell pool at the peak of immune response with memory population including TRM cells upon resolution of infection. We show that the T cells including T helper 1 cells (TH1) and mixed memory TH1 expressing high levels of TH1-associated transcription factor T-bet seed TRM cells. We and others have previously demonstrated that T-bet is important for TH1 differentiation and survival in LCMV infection. Here, we show T-bet deficient LCMV-specific cells vs controls have impaired ability to form T cell memory including TRM cells in the periphery. Further validating our cellular barcoding investigation that T-bet high expressing T cells seed TRM cells including memory cells and T-bet is crucial for the maintenance of immune memory. A better understanding of the pathways that dictate TRM formation is crucial for the development of both improved vaccines against pathogens and new therapeutics for malignancies.