title: Generation of dendritic cells from rabbit bone marrow mononuclear cell cultures supplemented with hGM-CSF and hIL-4.
abstract: The in vitro generation of dendritic cells (DCs) from either blood or bone marrow has been accomplished for humans and a number of other species. This ability has facilitated the opportunity to test the efficacy of DC vaccines in various tumor models. The cottontail rabbit papillomavirus (CRPV) model is the most clinically relevant animal model for human papillomavirus (HPV)-associated carcinogenesis. The CRPV model has been used to test various preventative and therapeutic vaccination strategies, and the availability of rabbit DCs would further expand its utility. However, to date, rabbit DCs have not been phenotypically and/or functionally characterized. Here we show that DCs can be generated in vitro from rabbit bone marrow mononuclear cells (BMMCs) cultured in the presence of the human cytokines GM-CSF and IL-4 and matured with lipopolysaccharide (LPS). These cells show upregulation of MHC class II and CD86, as well as downregulation of CD14, do not have non-specific esterase activity, are able to perform receptor-mediated endocytosis, and are potent stimulators of allogeneic T cell proliferation in mixed lymphocyte reactions. The ability to generate rabbit DCs makes it possible to test the efficacy of DC vaccination in the prevention and treatment of CRPV-induced lesions, which may provide useful preclinical data regarding the use of DC vaccines for HPV-associated lesions, including cervical cancer.
authors.affiliation: Department of Dermatology, Yale University School of Medicine, LCI 501, 333 Cedar Street, New Haven, CT 06520, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Cody
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
authors.forename: Mark
authors.initials: M
authors.lastname: Shlyankevich
authors.forename: Robert E
authors.initials: RE
authors.lastname: Tigelaar
authors.forename: Janet L
authors.initials: JL
authors.lastname: Brandsma
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Hanlon
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry / Q000662:veterinary; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D015847:Interleukin-4 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008858:Microscopy, Phase-Contrast / Q000662:veterinary; D011817:Rabbits
chemical_list: D015703:Antigens, CD; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor