Oral Presentation CD1-MR1 2024

A comparison of human unconventional T cell development (#57)

Daniel G Pellicci 1 2 , Naeimeh Tavakolinia 3 , Louis Perriman 3 4 5 , Sedi Jalali 3 , Stuart P Berzins 2 4 5
  1. Infection, Immunity and Global Health, Murdoch Children's Research Institute , Parkville, Melbourne, Vic, Australia
  2. University of Melbourne, Parkville, VIC, Australia
  3. Murdoch Children's Research Institute, Parkville, Melbourne, VIC, Australia
  4. Federation University , Ballarat, Victoria, Australia
  5. Fiona Elsey Cancer Research Institute, Ballarat, Australia

Unconventional T cells play important roles in cancer, infection and autoimmunity, although the factors that influence their frequency, development and function are still unclear. Our research has been at the forefront of understanding how functional unconventional T cells develop within the human thymus, first describing MAIT cell development (Koay et al., Nature Immunology 2016 & Koay et al., Science Immunology 2019) and more recently defining the postnatal thymic development of Vd2+ gamma delta T cells (Perriman et al., Science Immunology 2023). Here, we define the thymic development of human NKT cells, identifying a four-stage pathway that shares some similarities with MAIT cell and Vd2+ gamma delta T cell development, but we also identify important differences in these three development pathways. Further, the development of human NKT cells is distinct from mouse NKT cells, with limited functional repertories of NKT cells in human thymus and blood. Our work sheds important new light on human unconventional T development and may lead to new opportunities to influence the development of these cells to treat human disease.