Project R-2335

Dendritic cells as mediators of regulatory T-cell processes in multiple sclerosis (Research)

Dendritic cells (DC) belong to the innate immunity and are widely know as professional antigen presenting cells. Due to their specialized antigen presenting capacity an important link is provided to the adaptive immune system where they regulate the balance between immunity and tolerance. Recent studies have shown that DC can control autoreactive T cells and even induce regulatory T cells. Moreover there is evidence for a bidirectional interaction between regulatory T cells and DC. Biomed already demonstrated that CD4+CD25+ regulatory T cells are less functional in patients with multiple sclerosis (MS), but the cause of this remains still unknown. Due to the correlation between DC and regulatory T cells it can be speculated that a disturbance in one cell type has it consequence on the other, ultimately leading to the induction or perpetuation of an autoimmune disease like MS. Therefore this project will further investigate the role of DC in the pathogenesis of MS. In a first phase DC subsets are characterized on the basis of their phenotype, frequency and functionality between MS patients and healthy controls. A detailed insight into the characteristics of DC en their link with regulatory T cells in MS, can lead to new therapeutic strategies for the treatment of MS and other inflammatory diseases. In this regard, DC are generated out of bone marrow from mice and treated with different stimuli to obtain tolerogenic DC. In this second goal, tolerogenic DC will be screened for their capacity to induce regulatory T cells and counter autoreactive T cells. Lastly, tolerogenic DC will be used in an animal model for MS (EAE) to influence the disease process. Summarized this project tries to 1) find a disturbance in the DC/regulatory T cell balance in MS patients and 2) restore the immune balance in an animal model for MS.

01 January 2010 - 31 December 2013