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J Neuroinflammation. 2016 May 20;13(1):113. doi: 10.1186/s12974-016-0584-9.

Cryopreserved vitamin D3-tolerogenic dendritic cells pulsed with autoantigens as a potential therapy for multiple sclerosis patients.

Author information

1
Division of Immunology, Germans Trias i Pujol University Hospital and Research Institute, Campus Can Ruti, Badalona, Spain.
2
Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, 08193, Bellaterra (Cerdanyola del Vallès), Spain.
3
Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VAXINFECTIO), Antwerp University Hospital, Faculty of Medicine and Health Sciences, University of Antwerp, 2610, Wilrijk, Belgium.
4
Multiple Sclerosis Unit, Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
5
Division of Immunology, Germans Trias i Pujol University Hospital and Research Institute, Campus Can Ruti, Badalona, Spain. emmartinez.germanstrias@gencat.cat.
6
Department of Cellular Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, 08193, Bellaterra (Cerdanyola del Vallès), Spain. emmartinez.germanstrias@gencat.cat.

Abstract

BACKGROUND:

Tolerogenic dendritic cells (tolDC) have been postulated as a potent immunoregulatory therapy for autoimmune diseases such as multiple sclerosis (MS). In a previous study, we demonstrated that the administration of antigen-specific vitamin D3 (vitD3) tolDC in mice showing clinical signs of experimental autoimmune encephalomyelitis (EAE; the animal model of MS) resulted in abrogation of disease progression. With the purpose to translate this beneficial therapy to the clinics, we have investigated the effectivity of vitD3-frozen antigen-specific tolDC pulsed with myelin oligodendrocyte glycoprotein 40-55 peptide (f-tolDC-MOG) since it would reduce the cost, functional variability and number of leukapheresis to perform to the patients.

METHODS:

Mice showing EAE clinical signs were treated with repetitive doses of f-tolDC-MOG. Tolerogenic mechanisms induced by the therapy were analysed by flow cytometry and T cell proliferation assays.

RESULTS:

Treatment with f-tolDC-MOG was effective in ameliorating clinical signs of mice with EAE, inhibiting antigen-specific reactivity and inducing Treg. In addition, the long-term treatment was well tolerated and leading to a prolonged maintenance of tolerogenicity mediated by induction of Breg, reduction of NK cells and activation of immunoregulatory NKT cells.

CONCLUSIONS:

The outcomes of this study show that the use of antigen-specific f-tolDC promotes multiple and potent tolerogenic mechanisms. Moreover, these cells can be kept frozen maintaining their tolerogenic properties, which is a relevant step for their translation to the clinic. Altogether, vitD3 f-tolDC-MOG is a potential strategy to arrest the autoimmune destruction in MS patients.

KEYWORDS:

Breg; EAE; Multiple sclerosis; NK cells; NKT cells; Tolerogenic dendritic cells; Treg

PMID:
27207486
PMCID:
PMC4874005
DOI:
10.1186/s12974-016-0584-9
[Indexed for MEDLINE]
Free PMC Article

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