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T cell regulation, development and plasticity under lymphopenic conditions

Thursday 2 July 2015

Femke van Wijk

T cell regulation, development and plasticity under lymphopenic conditions
The second research line focuses on T cell regulation, development and plasticity in lymphopenic settings.
I

Elucidate T cell dynamics development and function following ASCT for autoimmune disease
The only therapy so far that can induce a long-term drug-free remission in refractory JIA but also in other autoimmune diseases such as Type I Diabetes, Systemic Sclerosis, and Crohn’s disease is autologous stem cell transplantation (aSCT). How the transplants are exactly rewiring a faulty immune system is still elusive We study the immune mechanisms underlying autologous stem cell transplantation (ASCT) for autoimmune diseases in both an experimental arthritis model and humans (Blood 2008, Arthritis & Rheumatology 2014, Ann Rheum Dis 2014).We are collaborating in a clinical trial study led by Dr. Bas Oldenburg and Dr. Herma Fidder (UMCU Gastroenterology) on autologous stem cell transplantation in refractory Crohn’s disease patients.

II Unravel the role of the thymus in T cell dynamics development and function in children
To get further insights into the development and plasticity of T cell regulation we collaborate with the pediatric IC/cardiology departments (Dr. K Jansen). An interesting group of patients are young children that undergo heart surgery in the first weeks of life. With this procedure the thymus is removed leading to a T cell lymphopenia as observed following aSCT. The difference is that there is no longer a thymus present. We have found that Treg preferentially proliferate following thymectomie, leading to a skewing in Treg subsets (JACI 2014). In a long term follow-up of these patients (the first surgeries have been performed in the late 1970) In this project we study aging and development of the T cell compartment.


Techniques: Flow cytomertry, RNA-seq, tissue cell isolation, T cell calcium fluxes, Functional T cell assays