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Myelin ingestion alters macrophage antigen-presenting function in vitro and in vivo
Marloes van Zwam1, Janneke N Samsom, Edward E Nieuwenhuis
1Department of Immunology, University Medical Center, P.O. Box 2040, Rotterdam, Zuid-Holland 3000 CA, the Netherlands. marloesvanzwam@hotmail.com
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.
Insights
Myelin-laden macrophages in multiple sclerosis (MS) can present antigens to T cells, potentially influencing disease. These macrophages limit autoimmune disease severity, suggesting a regulatory role.
Area of Science:
- Neuroimmunology
- Cellular Immunology
Background:
- Macrophages phagocytose myelin during multiple sclerosis (MS).
- The antigen-presenting capacity of myelin-laden macrophages and their role in MS pathogenesis remain unclear.
Purpose of the Study:
- To investigate whether myelin-laden macrophages can present antigens to T cells.
- To determine the functional consequences of myelin uptake by macrophages in the context of autoimmune disease.
Main Methods:
- In vitro generation of human and mouse myelin-laden macrophages.
- Assessment of major histocompatibility complex (MHC) class I and II and costimulatory molecule expression.
- Analysis of antigen uptake and T cell proliferation assays (naïve and memory T cells).
- In vivo studies in mouse models of experimental autoimmune encephalomyelitis (EAE).
Main Results:
- Myelin-laden macrophages express MHC class I/II and costimulatory molecules, indicating antigen-presenting capability.
- Human myelin-laden macrophages efficiently endocytose antigens and stimulate T cell proliferation.
- Mouse myelin-laden macrophages induce antigen-specific CD4(+) T cell proliferation in vivo, with transiently reduced IFN-γ release.
- Myelin-laden macrophages loaded with MOG peptide reduced EAE severity in mice.
Conclusions:
- Myelin uptake induces macrophages with retained antigen-presenting capacity.
- These macrophages play a role in limiting autoimmune-mediated disease, potentially offering therapeutic insights for MS.
