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

M van Zwam, JN Samsom… - Journal of leukocyte …, 2011 - academic.oup.com
M van Zwam, JN Samsom, EE Nieuwenhuis, MJ Melief, AF Wierenga-Wolf, IE Dijke…
Journal of leukocyte biology, 2011academic.oup.com
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 …
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.
Oxford University Press