Inflammatory DCs fail to present antigen but provide a crucial source of IL-12 in priming Th1 responses to CpG based vaccines. (P4514)

Abstract

Abstract DCs govern the induction of antigen specific adaptive immunity and thus constitute the main targets of novel vaccine approaches. Classical steady state DCs consist of multiple subsets, differing in their capacity to respond to TLR stimulation and to present antigen to CD4 and CD8 T cells. Under inflammatory conditions, an additional subset of monocyte derived inflammatory DCs (iDCs) arises. Although the innate role of iDCs in antimicrobial immunity is now clearly established, their role in directing the adaptive response is less evident. Immunization with OVA combined with the TLR9 agonist CpG resulted in the fast recruitment of CCR2 CD64 Ly6Chi CD11bhi monocytes to the draining lymph nodes, where they gradually adopt a CD11cint MHCIIint phenotype. Although a large fraction of these iDCs were OVA+, sorted iDCs failed to present the antigen to OT-I and OT-II T cells. Instead, antigen presentation was limited to migratory DCs. iDCs however proved to be the major source the Th1 polarising cytokine IL12. To investigate the role of iDC-derived IL12 in priming Th1 responses, mixed CCR2-/- /IL12-/- bone marrow chimaeras were immunized with OVA/CpG. In these chimaeras, solely IL12-/- iDCs can reach the lymph node, while classical lymph node DCs are fully competent of producing IL12. When compared to control WT/IL12-/- chimaeras, CCR2 -/-/IL12-/- mice displayed dramatically reduced Th1 responses, establishing the crucial role of iDCs in priming Th1 responses.