title: Stroma-dependent development of two dendritic-like cell types with distinct antigen presenting capability.
abstract: Novel antigen presenting cells (APCs) have been described in the murine spleen. Cells have a distinct CD11c(lo)CD11b(hi)MHC-II(-)CD8α(-) phenotype as highly endocytic dendritic-like cells that cross-present antigen to CD8(+) T cells but fail to activate CD4(+) T cells. These cells are named "L-DCs" because they reflect dendritic cells (DCs) produced in long-term spleen cultures (LTC). Similar cells were produced when bone marrow progenitors were cocultured over the splenic stromal line 5G3. Cocultures continuously produced a majority of L-DCs and a transient population of cells reflecting conventional dendritic cells (cDCs). Both the L-DC and cDC-like subsets cross-present antigen to CD8(+) T cells, inducing their activation and proliferation. However, as MHC-II(-) cells, L-DCs are unable to activate CD4(+) T cells, while MHC-II(+) cDC-like cells present antigen for CD4(+) T cell activation. These results distinguish two APC subsets produced in vitro: a transient population of cDC-like cells and L-DCs that are continuously produced, presumably from self-renewing progenitors. These subsets are not developmentally linked via a precursor or progeny relationship. L-DCs and cDC-like cells are also distinct in terms of cytokine expression, with 65 of 84 tested genes displaying greater than a twofold difference by quantitative reverse-transcriptase polymerase chain reaction. Splenic stroma supports production of two APC subsets reflecting different lineage origins.
authors.affiliation: Research School of Biology, Australian National University, Canberra, Australia.
authors.forename: Pravin
authors.initials: P
authors.lastname: Periasamy
authors.forename: Helen C
authors.initials: HC
authors.lastname: O'Neill
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D039481:CD11b Antigen / Q000276:immunology / Q000378:metabolism; D039521:CD11c Antigen / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D045142:Cross-Priming / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D039481:CD11b Antigen; D039521:CD11c Antigen; D016207:Cytokines; D000949:Histocompatibility Antigens Class II