The role of antigen-specific regulatory T cells in rheumatoid arthritis
Tuesday 5 May 2009
Prof.dr Willem van Eden and dr Femke Broere
Rheumatoid arthritis (RA) affects approximately 1% of the population worldwide. In the last few years it has become increasingly clear that T cells play a crucial role in the induction of arthritis, however other cells like B cells and macrophages are also important during the progression of disease. Our research project focuses on the role of joint antigen specific T-cells in arthritis and addressing the possibilities to use antigen specific T-cells to target disease suppressive regiments to inflamed joints.
Heat Shock Protein (HSP) 70 has been shown to modulate chronic inflammatory diseases. Immunization or nasal treatment with HSP70 (peptides) can protect animals from proteoglycan induced rheumatoid arthritis (PGIA). In previous studies it has been shown that modulation of experimentally induced arthritis was associated with the presence of IL-10.
IL-10 producing regulatory T cells (Tregs) might be responsible for the modulation of rheumatoid arthritis (RA). Tregs maintain peripheral tolerance and absence of Tregs is associated with autoimmunity. Tregs express the transcription factor FoxP3 and can be identified by the expression of CD4 and CD25. Their mechanisms of action can be broad and seems to be dependent on TCR specificity and the local environment.
We hypothesize that the presence of HSP-specific regulatory T cells can modulate disease in an IL-10 dependent manner. We study these cell in vitro by looking at suppressive capacity of the cells (in vitro suppression assay), cytokine production (by Luminex or Elispot), expression of Treg-associated proteins (by FACS) or genes (Real time PCR). We also examine the role of antigen-specific Tregs in our mouse model for arthritis. For this we isolate HSP-specific Tregs (FACSsort) and transfer these cells into recipient mice with arthritis. Suppression of disease can then be assessed, followed by in vitro assays (see above) and analysis of joint inflammation (immunohistochemistry).
For the current study the following projects are available:
- Tracking of transferred regulatory T cells by Thy1.1 and FoxP3-GFP expression
- Setup detection assay of antigen-specific regulatory T cells (T cell capture), as well as histology for the localization of transferred regulatory T cells
- Examine if induced Tregs or natural Tregs are responsible for modulation of arthritis
Cell culture, FACS analysis, Cytokine analysis assays (Luminex,, ELIspot) and Real time PCR, Laboratory animal handling, Immunohistochemistry
6 or 9 months
Dr Femke Broere, firstname.lastname@example.org, 030-253 1872