Antigen Presenting Properties of a Myeloid Dendritic-Like Cell in Murine Spleen

Abstract

This paper distinguishes a rare subset of myeloid dendritic-like cells found in mouse spleen from conventional (c) dendritic cells (DC) in terms of phenotype, function and gene expression. These cells are tentatively named “L-DC” since they resemble dendritic-like cells produced in longterm cultures of spleen. L-DC can be distinguished on the basis of their unique phenotype as CD11bhiCD11cloMHCII-CD43+Ly6C-Ly6G-Siglec-F- cells. They demonstrate similar ability as cDC to uptake and retain complex antigens like mannan via mannose receptors, but much lower ability to endocytose and retain soluble antigen. While L-DC differ from cDC by their inability to activate CD4+ T cells, they are capable of antigen cross-presentation for activation of CD8+ T cells, although less effectively so than the cDC subsets. In terms of gene expression, CD8- cDC and CD8+ cDC are quite distinct from L-DC. CD8+ cDC are distinguishable from the other two subsets by expression of CD24a, Clec9a, Xcr1 and Tlr11, while CD8- cDC are distinguished by expression of Ccnd1 and H-2Eb2. L-DC are distinct from the two cDC subsets through upregulated expression of Clec4a3, Emr4, Itgam, Csf1r and CD300ld. The L-DC gene profile is quite distinct from that of cDC, confirming a myeloid cell type with distinct antigen presenting properties.

A novel myeloid cell in murine spleen defined through gene profiling

“…70 All of these genes reflect the function of APC and are consistent with the defined functional role of "L-DC" in CD8 + T cell activation and cytotoxic function. 16,17 Consistent with the reports in the literature, resident monocytes expressed Ly6c1, Ly6c2 and Ccr2 ( Figure 4A). 9,41 Expression of Ly6C1/2 reflects the sorting strategy used here, whereby resident monocytes were separated from "L-DC" ( Table 1).…”

“…The clearly defined populations of resident monocytes, inflammatory monocytes, eosinophils, CD8 + cDC and CD8 − cDC were sorted from spleens of C57BL/6J mice according to the staining procedure developed previously (Table 1). 15,16…”

“…It was also clearly distinguished from the main splenic DC subsets . In terms of antigen presenting capacity, this novel subset is superior in capacity to cross‐present antigen to CD8 T cells and to activate cytotoxic function, although incapable of activating of CD4 T cells . These cells were shown by gene profiling to reflect a distinct cell type expressing genes common to both myeloid and dendritic lineages .…”

“…However, through a series of studies dissecting the myeloid cell populations in both murine and human spleen, this novel splenic subset has been identified and analysed in terms of function equivalent to the in vitro‐derived cell type. The “L‐DC” subset in mice has been shown to be phenotypically distinct from the four splenic macrophage subsets, and both phenotypically and functionally distinct from the two splenic monocyte subsets . It was also clearly distinguished from the main splenic DC subsets .…”

“…16 These cells were shown by gene profiling to reflect a distinct cell type expressing genes common to both myeloid and dendritic lineages. 16 This novel subset closely resembles dendritic-like cells produced in vitro in long-term cultures of spleen (LTC-DC) and similar cells produced in co-cultures of bone marrow progenitors over splenic stromal lines. 20,[25][26][27] For this reason alone, it has been referred to as "L-DC" in these studies.…”