Myelin ingestion alters macrophage antigen-presenting function in vitro and in vivo

Journal of Leukocyte Biology

Marie-José Melief¹  Jon D. Laman ¹  Marjan van Meurs¹  Jane S. Voerman¹  I. Esmé Dijke¹  Leonie A. Boven  and¹  Annet F. Wierenga-Wolf¹  Simone Talens¹  Janneke N. Samsom¹  Marloes van Zwam ¹  Edward E. Nieuwenhuis¹ 

[1] Departments of Immunology and Hematology, Erasmus MC, University Medical Center,  MS Centre Erasmus, and Division of Pediatric Gastroenterology, Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands

关键词: monocytes;    Th1/Th2 cells;    antigen presentation/processing;    EAE/MS;    neuroimmunology;   

DOI  :  10.1189/jlb.1209813

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown