Human autoimmune diseases such as reumatoid arthritis (RA) and multiple sclerosis (MS) are believed to develop when self-tolerance mechanisms are failing, with a chronic destructive inflammation as result. To experimentally study autoimmunity, we have used murine models that mimic their human counterparts; experimental autoimmune encephalomyelitis (EAE) – a model for MS, and collagen induced arthritis (CIA) and antigen induced arthritis (AIA) – models for RA.
A sub-population of T cells, termed natural killer T cells (NKT), have been suggested as having immunoregulatory features in pathogenic autoimmunity. How NKT cells are activated to perform this regulation and by which functional pathways they act is not completely understood. A number of natural antigens activating NKT cells via the antigen presenting molecule CD1d have so far been identified as glycolipids originating from either bacteria or self.
This thesis investigates the role of NKT cells in autoimmune tissue-specific inflammation. We found that NKT cells can down-regulate both the central nervous system-specific autoimmunity in EAE, and the joint-specific inflammation in experimentally induced arthritis. We also show data indicating that this regulation requires activation in the periphery, and we have identified a natural self-peptide capable of exerting this activation; A CD1d restricted peptide derived from autologous collagen type II. By vaccinating mice with this peptide we were able to ameliorate the inflammation and reduce the disease phenotype in both CIA and EAE. We also found the peptide-specific NKT cells capable of suppressing activated T cells in vitro. Taken together, this thesis show that CD1d restricted NKT cells can be activated to down-regulate pathogenic autoimmunity, and should be investigated as targets for future autoimmune therapies.
- Department of Clinical Sciences, Lund
- Issazadeh, Shohreh, Supervisor
- Siesjö, Peter, Supervisor
|Award date||2014 Mar 4|
|Publication status||Published - 2014|
Place: Neuroakademiens föreläsningssal, EA, blocket plan 4
Name: Cardell, Susanna
Affiliation: Gothenburg University
- NKT cells
- CD1d antigen presentation
- Multiple sclerosis
- Rheumatoid arthritis