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Open Access

Tolerogenic dendritic cells in experimental autoimmune encephalomyelitis, specific tolerance induction?

  • Carla Sellés-Moreno1, 2, 4,
  • Cristina Ramo-Tello2,
  • Laia Grau-López2,
  • Ricardo Pujol-Borrel3, 4 and
  • Eva M Martínez-Cáceres1, 4
Journal of Translational Medicine201210(Suppl 3):P27

https://doi.org/10.1186/1479-5876-10-S3-P27

Published: 28 November 2012

Keywords

Multiple SclerosisExperimental Autoimmune EncephalomyelitisPertussisEncephalomyelitisPertussis Toxin

Background

Specific cell therapy with tolerogenic Dendritic Cells (tolDCs) loaded with autoantigens is a promising tool for the attenuation of pathogenic T cells in autoimmune diseases such as Multiple Sclerosis (MS).

The aim of this study was to analyse the in vitro effect of tolerogenic bone marrow derived DCs (BM-DCs) loaded with Myelin Oligodendrocyte Glycoprotein (MOG)40-55 peptide from C57BL/6 mice, on the specific proliferation of splenocytes of mice with EAE.

Methods

Chronic EAE was induced in C57BL/6 mice by s.c. immunization with MOG40-55 emulsified in complete Freund's adjuvant. Pertussis Toxin was injected i.v. at days 0 and 2 post-immunization to increase blood-brain-barrier permeability. Clinical score was daily measured based on tail/leg paralysis.

TolBM-DCs were in vitro differenciated with GM-CSF in the presence of vitamin D3 (VD3) for 8 days.

On day 7, maturation was induced with LPS. Viability, efficiency of differentiation and phenotype of tolBM-DCs were evaluated. To assess antigen specificity, tolBM-DCs were pulsed with MOG40-55, after the maturation stimulus (day 7) for 18h and cocultured with syngeneic splenocytes from mice with established EAE.

Results

TolBM-DCs displayed a semi-mature phenotype, exhibited by low levels of MHC class II and coestimulatory molecules (CD40, CD86) compared to control mature BM-DCs (mBM-DCs) differenciated in the absence of VD3. MOG40-55 loaded TolDCs showed to be poor stimulators of specific T cells of mice with EAE, compared to mBM-DCs.

Conclusion

These results suggest that MOG-loaded TolDCs may be a powerful tool to induce specific T-cell hyporesponsiveness in mice with chronic MOG-induced EAE. Hence, treatment with tolDCs loaded with myelin peptides might be a potential therapy for EAE/MS.

Authors’ Affiliations

(1)
Immunobiology Laboratory For Research And Diagnostic Applications (LIRAD-BST), Badalona, Spain
(2)
Multiple Sclerosis Unit, Dept. of Neurosciences, Germans Trias i Pujol University Hospital (HUGTiP) and Health Science Research Institute (IGTP), Badalona, Spain
(3)
Dept. of Immunology, Hospital Vall d’Hebron, Barcelona, Spain
(4)
Universitat Autònoma Barcelona, (UAB), Spain

Copyright

© Sellés-Moreno et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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