title: CD11c-positive cells from brain, spleen, lung, and liver exhibit site-specific immune phenotypes and plastically adapt to new environments.
abstract: The brain's immune privilege has been also attributed to the lack of dendritic cells (DC) within its parenchyma and the adjacent meninges, an assumption, which implies maintenance of antigens rather than their presentation in lymphoid organs. Using mice transcribing the green fluorescent protein under the promoter of the DC marker CD11c (itgax), we identified a juxtavascular population of cells expressing this DC marker and demonstrated their origin from bone marrow and local microglia. We now phenotypically compared this population with CD11c/CD45 double-positive cells from lung, liver, and spleen in healthy mice using seven-color flow cytometry. We identified unique, site-specific expression patterns of F4/80, CD80, CD86, CX3CR1, CCR2, FLT3, CD103, and MHC-II. Furthermore, we observed the two known CD45-positive populations (CD45(high) and CD45(int) ) in the brain, whereas liver, lung, and spleen exhibited a homogeneous CD45(high) population. CD11c-positive microglia lacked MHC-II expression and CD45(high) /CD11c-positive cells from the brain have a lower percentage of MHC-II-positive cells. To test whether phenotypical differences are fixed by origin or specifically develop due to environmental factors, we transplanted brain and spleen mononuclear cells on organotypic slice cultures from brain (OHSC) and spleen (OSSC). We demonstrate that adaption and ramification of MHC-II-positive splenocytes is paralleled by down-regulation of MHC-II, whereas brain-derived mononuclear cells neither ramified nor up-regulated MHC-II in OSSCs. Thus, brain-derived mononuclear cells maintain their MHC-II-negative phenotype within the environment of an immune organ. Intraparenchymal CD11c-positive cells share immunophenotypical characteristics of DCs from other organs but remain unique for their low MHC-II expression.
authors.affiliation: Institute of Anatomy, Leipzig University, Leipzig, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Immig
authors.forename: Martin
authors.initials: M
authors.lastname: Gericke
authors.forename: Franziska
authors.initials: F
authors.lastname: Menzel
authors.forename: Felicitas
authors.initials: F
authors.lastname: Merz
authors.forename: Martin
authors.initials: M
authors.lastname: Krueger
authors.forename: Fridtjof
authors.initials: F
authors.lastname: Schiefenhövel
authors.forename: Andreas
authors.initials: A
authors.lastname: Lösche
authors.forename: Kathrin
authors.initials: K
authors.lastname: Jäger
authors.forename: Uwe-Karsten
authors.initials: UK
authors.lastname: Hanisch
authors.forename: Knut
authors.initials: K
authors.lastname: Biber
authors.forename: Ingo
authors.initials: I
authors.lastname: Bechmann
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D001921:Brain / Q000166:cytology*; D039521:CD11c Antigen / Q000378:metabolism*; D000073883:CX3C Chemokine Receptor 1; D003713:Dendritic Cells / Q000378:metabolism*; D005434:Flow Cytometry; D005802:Genes, MHC Class II / Q000235:genetics; D049452:Green Fluorescent Proteins; D039001:Integrin alpha Chains / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008099:Liver / Q000166:cytology*; D008168:Lung / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism*; D054390:Receptors, CCR2 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D013154:Spleen / Q000166:cytology*; D051941:fms-Like Tyrosine Kinase 3 / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D039521:CD11c Antigen; D000073883:CX3C Chemokine Receptor 1; C497965:Cd86 protein, mouse; C471885:Cx3cr1 protein, mouse; D039001:Integrin alpha Chains; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; C091367:alpha E integrins; C036763:monocyte-macrophage differentiation antigen; D049452:Green Fluorescent Proteins; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3; D017493:Leukocyte Common Antigens
keywords: Key words CD11c-positive cells; immune privilege; microglia