Abstract

Dendritic cells (DCs) are well known as professional antigen-presenting cells (APC) able to initiate specific T-cell responses to pathogens in lymph nodes (LN) draining the site of infection. However, the respective contribution of migratory and LN-resident DCs in this process remains unclear. As DC subsets represent important targets for vaccination strategies, more precise knowledge of DC subsets able to present vaccine antigens to T cells efficiently is required. To investigate the capacities of DCs migrating in the lymph (L-DCs) to initiate a specific T-cell response, we used physiologically generated DCs collected from a pseudoafferent lymphatic cannulation model in sheep. The CD1b+ L-DCs were assessed for presenting antigens from the vaccine attenuated strain of Salmonella enterica serovar Abortusovis. CD1b+ L-DCs were able to phagocytose, process and to present efficiently Salmonella antigens to effector/memory T cells in vitro. They were shown to be efficient APC for the priming of allogeneic naive T cells associated with inducing both IFN-γ and IL-4 responses. They were also efficient in presenting Salmonella antigens to autologous naive T cells associated with inducing both IFN-γ and IL-10 responses. The capacities of L-DCs to process and present Salmonella antigens to T cells were investigated in vivo after conjunctival inoculation of Salmonella. The CD1b+ L-DCs collected after inoculation were able to induce the proliferative response of CD4+ T cells suggesting the in vivo capture of Salmonella antigens by the CD1b+ L-DCs, and their potential to present them directly to CD4+ T cells. In this study, CD1b+ L-DCs present potential characteristics of APC to initiate by themselves T cell priming in the LN. They could be used as target cells for driving immune activation in vaccinal strategies.

Highlights

  • Dendritic cells (DCs) are well known as professional antigenpresenting cells (APC) able to initiate specific T-cell responses to pathogens in lymph nodes (LN) draining the site of infection

  • This study investigated the potential of migratory DCs to present Salmonella Ag directly to T cells in LN, by challenging the CD1b+ lymph DCs (L-DCs) to present Ag of a Salmonella vaccine strain to specific and naive T cells using an in vitro Ag presentation assay

  • Our results show that CD1b+ L-DCs alone are able to present Salmonella antigens to specific autologous effector/memory CD4+ T cells and to naive T cells associated with a combined IFN-c and IL-10 response

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Summary

Introduction

Dendritic cells (DCs) are well known as professional antigenpresenting cells (APC) able to initiate specific T-cell responses to pathogens in lymph nodes (LN) draining the site of infection. Numerous studies examining the role of migratory and LNresident DCs in the induction of CD8+ T cell-mediated immunity to viruses after cutaneous infection have shown the exclusive cross-presentation of Ag by CD8a+ DCs resident in LN, and the role of migratory DCs in delivering and transferring Ag to resident CD8a+ DCs [3]. These conclusions may not be applicable to the priming of cytotoxic T-lymphocyte (CTL) responses to all viruses since migratory skin DCs have been shown to present lentivirus-derived ovalbumin (OVA) directly to LN CD8+ T cells [6], or at least in cooperation with

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