Oral Presentation Lorne Infection and Immunity 2014

Cooperation between type I IFN and CD4+ T cell help in DC activation and IL-15-dependent priming of virus-specific CD8+ T cells (#40)

Marie Greyer 1 , Angus Stock 1 , Gayle M Davey 1 , Christina Tebarzt 1 , Justine D Mintern 1 , David Tscharke 2 , Julia Marchingo 3 , Philip D Hodgkin 3 , Stephen J Turner 1 , Thomas Gebhardt 1 , Francis R Carbone 1 , William R Heath 1 , Sammy Bedoui 1
  1. University of Melbourne, Melbourne, VIC, Australia
  2. Research School of Biology, The Australian National University , Canberra, NSW, Australia
  3. Immunology Devision, The Walter and Eliza Hall Institute of Medical Research, Melbourne , VIC, Australia

Control of intracellular pathogens relies on priming of cytotoxic CD8+ T cells by dendritic cells (DC), but how precisely DC are activated in the process and how they instruct CD8+ T cells to differentiate into effector cells remains unclear. We demonstrate that virus-specific CD8+ T cell priming depended on the sequential stimulation of CD8+ DC by type I IFN and CD4+ T cells, where type I IFN ‘conditioned’ DCs become receptive to CD40/CD40L-mediated CD4+ T cell help. This two-step activation endowed antigen presenting CD8+ DC with the capacity to transpresent IL-15 to naïve CD8+ T cells, without which these were unable to respond to IL-2 with high affinity and failed to undergo effector differentiation. These findings reveal a complex in vivo interplay between type I IFN and CD4+ T cells in DC activation and CD8+ T cell priming and indicate a role for CD4+ T cells as potent amplifiers of innate signals required for adaptive immune responses.