Anatomic location defines antigen presentation by dendritic cells to T cells in response to intravenous soluble antigens

Abstract

In the spleen, exogenous antigen is preferentially presented by CD8a + CD11b -DC to CD8 T cells and by CD8a -CD11b + DC to CD4 T cells. However, it is not yet clear whether the same rule applies to other secondary lymphoid organs. To address this issue, we first classified secondary lymphoid tissues into three categories based on the expression pattern of CD8a and CD11b in C57BL/6 and BALB/c mice: (a) spleen, (b) mesenteric lymph node (MLN) and (c) other peripheral lymph nodes (PLN). We then analyzed the OVA-specific T cell-stimulating capacity of each DC subset after intravenous injection with soluble OVA. Our results show that, regardless of tissue origin, CD8a -CD11b + DC generally present OVA to CD4 T cells, a finding that held true as well for CD8a + CD11b + DC in PLN. In striking contrast, CD8a + CD11b -DC in spleen, CD8a -CD11b + DC in MLN and CD8a + CD11b + DC in PLN mainly cross-present OVA to CD8 T cells in their respective tissues. Of note, CD8a -CD11b + DC in MLN and CD8a + CD11b + DC in PLN present OVA to both CD4 T and CD8 T cells. Therefore, the antigen-presenting capacity of each distinct DC subset is determined by its anatomic environment in combination with its surface phenotype.

The Relative Efficiency of Acquisition of MHC:Peptide Complexes and Cross-Presentation Depends on Dendritic Cell Type

“…As these observations suggest a difference in the ability of DC subsets to induce T cell responses following acquisition of Ag either via cross-presentation or MHC transfer we decided to investigate the stimulatory capacities of another subset of spleen derived DCs, the CD8␣ Ϫ DCs. These cells have recently been described as being inefficient at cross-presentation of soluble Ag in vivo (39). We also observed this in vitro (Fig.…”

Temporal changes in dendritic cell subsets, cross-priming and costimulation via CD70 control CD8+ T cell responses to influenza

“…Moreover, although CD8α + cDCs are the only DCs to cross-prime influenza-specific CD8 + T cells after intravenous or subcutaneous infection20, both CD8α + DCs and airway-derived CD8α − CD11b lo DCs prime CD8 + T cells after intranasal infection16. Even the ability of CD8α + DCs to cross-prime CD8 + T cells to soluble OVA depends on the lymphoid organ from which they are isolated43. Thus, cross-priming by DCs can be strongly influenced by how DCs acquire antigen and the type of antigen they encounter.…”

Defining the anatomical localisation of subsets of the murine mononuclear phagocyte system using integrin alpha X (Itgax, CD11c) and colony stimulating factor 1 receptor (Csf1r, CD115) expression fails to discriminate dendritic cells from macrophages

“…However these rules appear to vary dependent upon their anatomical localisation (McLellan et al 2002) especially within the lymph nodes, lung (Belz et al 2004) and Peyer's patch (Fleeton et al 2004). This classification system is further confused by the presence of both double positive and double-negative subsets in some lymphoid tissues with apparently overlapping functional abilities in terms of CD4 and CD8 T-cell presentation (Chung et al 2007). Other studies have suggested that true functional differences between DC subsets are best characterized by Cd8a expression or lack of amongst Itgax + cells.…”