The role of splenic CD103+CD8α+cDCs in the induction of CTL responses during respiratory virus infection (168.11)

Abstract

Abstract We have previously reported that large numbers of virus-specific CD8+ T cells were detected in the spleen following intranasal influenza virus infection. This finding does not seem simply due to the migration of cells from the draining mediastinal lymph nodes (mLN), but rather indicates that spleen can be a site for the induction of primary CTL responses. Although the integrin αEβ7 (CD103)+ migratory DCs have been known as a major DC subset which prime naïve influenza virus-specific CD8+ T cells in the mLN, what kind of DC subset is responsible for the induction of CTL responses in the spleen remains unclear. In this study, we found that increased numbers of CD103+DCs were detectable in the spleen following influenza virus infection, and the majority of CD103+DCs expressed CD8α. Although both CD103+CD11chi DCs (CD103+DCs) and CD103-CD11chi DCs (CD103-DCs) showed activated phenotype evidenced by the expression of co-stimulatory molecules at 9 days post infection, PDL-1 expression pattern was different between these two subsets. Immunohistochemical analysis showed that CD103+DCs localized in the T cell area (also in the B cell area) and purified CD103+DCs produced large amounts of IL-12p40 compared with CD103-DCs. These data suggest that splenic CD103+DCs may play a critical role in the development of CTL responses during influenza virus infection. We are currently investigating how efficiently splenic CD103+DCs act as antigen presenting cells.