Oral Presentation Australasian Society for Immunology Annual Scientific Meeting 2014

Temporal regulation of T cell priming and cellular dynamics during peripheral viral infection (#18)

Jyh Liang Hor 1 , Paul G Whitney 1 , Andrew G Brooks 1 , William R Heath 1 , Scott N Mueller 1
  1. Peter Doherty Institute, University of Melbourne, Parkville, VIC, Australia

The spatial and temporal dynamics of CD4 and CD8 T lymphocyte priming in the draining lymph nodes (LN) during peripheral viral infection in vivo is not clear. Unlike lymph-borne or systemic infection, migratory dendritic cells (DC) transporting antigen from periphery during localised infection are required to initiate a robust T cell response. During cutaneous herpes simplex virus (HSV-1) infection, LN-resident CD8a+ DC are the predominant DC subset that primes CD8 T cells, and require antigen transfer from migratory CD11b+ DC. The relative contribution of different DC subsets and their dynamic interactions with CD4 and CD8 T cells in vivo, as well as when and where CD4 T cells provide ‘help’ for CD8 T cell priming remain elusive. Following skin HSV-1 infection we observed differential priming kinetics between HSV-specific CD4 and CD8 T cells, whereby CD4 T cell activation preceded CD8 T cells by 12-24 hours. Priming occurred predominantly in T cell zones and the cortical ridge, rather than the LN periphery as found for lymph-borne infections. Intravital two-photon microscopy of the draining LN indicated early clustering of CD4 T cells primarily with migratory DC, which involved prolonged T-DC interactions. In contrast, CD8 T cells only established stable T-DC contact later and interacted with non-migratory DC. These data reveal unexpected temporal differences in the priming of T cell subsets and highlight the distinct roles of DC subsets following localised viral infection.