1. Vaccination with Flt3L-induced CD8α+ dendritic cells prevents CD4+ T helper cell-mediated experimental autoimmune myocarditis
- Author
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Peter P. Liu, Alan Valaperti, Mototsugu Nishii, Davide Germano, Urs Eriksson, University of Zurich, and Valaperti, Alan
- Subjects
CD4-Positive T-Lymphocytes ,Male ,3400 General Veterinary ,Peptide ,10052 Institute of Physiology ,Mice ,0302 clinical medicine ,Interferon ,2400 General Immunology and Microbiology ,Myosin ,Mice, Knockout ,chemistry.chemical_classification ,Mice, Inbred BALB C ,0303 health sciences ,biology ,Vaccination ,Interleukin ,T-Lymphocytes, Helper-Inducer ,T helper cell ,3. Good health ,Myocarditis ,Infectious Diseases ,medicine.anatomical_structure ,10076 Center for Integrative Human Physiology ,Molecular Medicine ,Antibody ,medicine.drug ,610 Medicine & health ,Autoimmune Diseases ,Interferon-gamma ,03 medical and health sciences ,medicine ,Animals ,Humans ,030304 developmental biology ,General Veterinary ,General Immunology and Microbiology ,business.industry ,Public Health, Environmental and Occupational Health ,Membrane Proteins ,2739 Public Health, Environmental and Occupational Health ,2725 Infectious Diseases ,Dendritic Cells ,Dendritic cell ,Disease Models, Animal ,chemistry ,1313 Molecular Medicine ,Immunology ,biology.protein ,570 Life sciences ,business ,030215 immunology - Abstract
Experimental autoimmune myocarditis (EAM) represents a CD4(+) T helper (Th) cell-mediated mouse model of inflammatory heart disease. Interferon (IFN)-γ, typically produced by Th1 cells, reduces EAM severity in myosin heavy-chain-(MyHC)-α peptide/Complete Freund adjuvant-immunized mice. Thus, developing a vaccination strategy that promotes differentiation of Th1 cells may be beneficial in EAM. FMS-like tyrosine kinase 3 ligand (Flt3L)-induced splenic CD8α(+) dendritic cells (DC), which produce interleukin (IL)-12p35, were identified to selectively induce biased differentiation towards Th1. Mice vaccinated with MyHC-α-loaded Flt3L-induced splenic CD8α(+) DC were protected from EAM. In contrast, when Flt3L-induced splenic CD8α(+) DC were pre-stimulated and over-activated with LPS and αCD40 antibodies or loaded with unspecific OVA(323-339) peptide instead of MyHC-α peptide, mice developed similar disease scores as non-vaccinated controls. Vaccination efficacy depended on IFN-γ, since CD8α(+)-vaccinated IFN-γR(-/-) mice were not protected. Importantly, splenic CD8α(+) vaccination was independent of regulatory T cells. Taken together, Flt3L-induced dendritic cell-based antigen-specific vaccination limits expansion of auto-reactive Th cells and protects mice from autoimmune heart inflammation.
- Published
- 2013
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