1. CD11b+ monocytes abrogate Th17 CD4+ T cell-mediated experimental autoimmune myocarditis
- Author
-
Przemyslaw Blyszczuk, Christian Mueller, Urs Eriksson, Alan Valaperti, Stefan Dirnhofer, Chen Dong, Davide Germano, René R. Marty, Nora Mauermann, Lukas Hunziker, Gabriela Kania, Bernd M. Leimenstoll, University of Zurich, and Eriksson, U
- Subjects
CD4-Positive T-Lymphocytes ,T cell ,Immunology ,Molecular Sequence Data ,Inflammation ,Mice, Transgenic ,610 Medicine & health ,Cell Separation ,Lymphocyte Depletion ,Monocytes ,Autoimmune Diseases ,Cell Line ,Mice ,In vivo ,Cell Movement ,medicine ,Immunology and Allergy ,Animals ,Amino Acid Sequence ,Feedback, Physiological ,Mice, Knockout ,Mice, Inbred BALB C ,2403 Immunology ,CD11b Antigen ,biology ,business.industry ,Immune Sera ,Interleukin-17 ,Th1 Cells ,medicine.disease ,In vitro ,Mice, Mutant Strains ,Myocarditis ,medicine.anatomical_structure ,Immunization ,Integrin alpha M ,Cell culture ,biology.protein ,Disease Progression ,10209 Clinic for Cardiology ,2723 Immunology and Allergy ,medicine.symptom ,business ,Progressive disease - Abstract
Experimental autoimmune myocarditis (EAM) represents a Th17 T cell-mediated mouse model of postinflammatory heart disease. In BALB/c wild-type mice, EAM is a self-limiting disease, peaking 21 days after alpha-myosin H chain peptide (MyHC-alpha)/CFA immunization and largely resolving thereafter. In IFN-gammaR(-/-) mice, however, EAM is exacerbated and shows a chronic progressive disease course. We found that this progressive disease course paralleled persistently elevated IL-17 release from T cells infiltrating the hearts of IFN-gammaR(-/-) mice 30 days after immunization. In fact, IL-17 promoted the recruitment of CD11b(+) monocytes, the major heart-infiltrating cells in EAM. In turn, CD11b(+) monocytes suppressed MyHC-alpha-specific Th17 T cell responses IFN-gamma-dependently in vitro. In vivo, injection of IFN-gammaR(+/+)CD11b(+), but not IFN-gammaR(-/-)CD11b(+), monocytes, suppressed MyHC-alpha-specific T cells, and abrogated the progressive disease course in IFN-gammaR(-/-) mice. Finally, coinjection of MyHC-alpha-specific, but not OVA-transgenic, IFN-gamma-releasing CD4(+) Th1 T cell lines, together with MyHC-alpha-specific Th17 T cells protected RAG2(-/-) mice from EAM. In conclusion, CD11b(+) monocytes play a dual role in EAM: as a major cellular substrate of IL-17-induced inflammation and as mediators of an IFN-gamma-dependent negative feedback loop confining disease progression.
- Published
- 2008
- Full Text
- View/download PDF