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
Summary
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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