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

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.

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Correspondence to Carla Sellés-Moreno.

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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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Sellés-Moreno, C., Ramo-Tello, C., Grau-López, L. et al. Tolerogenic dendritic cells in experimental autoimmune encephalomyelitis, specific tolerance induction?. J Transl Med 10, P27 (2012). https://doi.org/10.1186/1479-5876-10-S3-P27

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Keywords

  • Multiple Sclerosis
  • Experimental Autoimmune Encephalomyelitis
  • Pertussis
  • Encephalomyelitis
  • Pertussis Toxin