title: Myelin ingestion alters macrophage antigen-presenting function in vitro and in vivo.
abstract: During MS, phagocytosing myelin-containing macrophages arise and lie in close proximity to T cells. To date, it has not been addressed whether these myelin-laden macrophages have the capacity to present antigens to T cells and whether this contributes to inflammation in disease. We demonstrate that in vitro-generated human and mouse myelin-laden macrophages expressed MHC class I and II and costimulatory molecules and are thus well equipped for antigen presentation. Human myelin-laden macrophages exhibited normal endocytosis of particulate and soluble antigens. In addition, human myelin-laden macrophages elicited active T cell proliferation of naïve as well as memory T cells. Furthermore, mouse myelin-laden macrophages induced primary antigen-specific CD4(+) T cell proliferation in vivo but transiently diminished IFN-γ release. Functionally, MOG peptide-loaded myelin-laden mouse macrophages modestly but significantly reduced the severity of MOG peptide-induced EAE. These data show that myelin uptake results in the induction of a population of macrophages that retains antigen-presenting capacity and limits autoimmune-mediated disease.
authors.affiliation: Department of Immunology, University Medical Center, P.O. Box 2040, Rotterdam, Zuid-Holland 3000 CA, the Netherlands. marloesvanzwam@hotmail.com
authors.forename: Marloes
authors.initials: M
authors.lastname: van Zwam
authors.forename: Janneke N
authors.initials: JN
authors.lastname: Samsom
authors.forename: Edward E
authors.initials: EE
authors.lastname: Nieuwenhuis
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Melief
authors.forename: Annet F
authors.initials: AF
authors.lastname: Wierenga-Wolf
authors.forename: I Esmé
authors.initials: IE
authors.lastname: Dijke
authors.forename: Simone
authors.initials: S
authors.lastname: Talens
authors.forename: Marjan
authors.initials: M
authors.lastname: van Meurs
authors.forename: Jane S
authors.initials: JS
authors.lastname: Voerman
authors.forename: Leonie A
authors.initials: LA
authors.lastname: Boven
authors.forename: Jon D
authors.initials: JD
authors.lastname: Laman
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000276:immunology*; D009186:Myelin Sheath / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II