During MS, phagocytosing myelin-containing macrophages arise and lie in close proximity to T cells. To date, it has not been addressed whether these myelinladen 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.uman myelin-laden macrophages exhibited normal endocytosis of particulate and soluble antigens. In addition, human myelin-laden macrophages elicited active T cell proliferation of nai{dotless}̈ve 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.

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Keywords Antigen presentation/processing, EAE/MS, Monocytes, Neuroimmunology, Th1/Th2 cells
Persistent URL dx.doi.org/10.1189/jlb.1209813, hdl.handle.net/1765/26691
Journal Journal of Leukocyte Biology
van Zwam, M, Samsom, J.N, Nieuwenhuis, E.E.S, Melief, M.J, Wierenga-Wolf, A.F, Dijke, I.E, … Laman, J.D. (2011). Myelin ingestion alters macrophage antigen-presenting function in vitro and in vivo. Journal of Leukocyte Biology, 90(1), 123–132. doi:10.1189/jlb.1209813