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Can functional regulatory T cells (Treg) be induced in peripheral blood from humans and used for therapy in immune disorders?

Thursday 16 April 2009

CD4+ Treg can suppress activation of other T cells and therefore they are important for immune regulation. Treg express the transcription factor FOXP3. People with a defect in FOXP3 suffer from a severe disease called IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome).

Furthermore it is shown in several animal models but also in humans that the presence of Treg can influence the course of autoimmune disease.

Our research focuses on how to manipulate Treg. The reason is that Treg are potential targets to decrease for instance autoimmunity.

Heat Shock Protein 60 (HSP60) is naturally expressed upon stress and therefore present at sites of inflammation. In our group we found that the T cell reactivity to HSP60 correlates with disease remission in Juvenile Idiopathic Arthritis1. Therefore we hypothesized that HSP60 can induce Treg.

We found indeed that we can induce FOXP3 expressing Treg from CD4+ non-Treg in vitro with HSP602.

Currently we are investigating the mechanism of HSP60 mediated Treg induction.

Furthermore if we want to use induced Treg to modulate disease, it is essential to show at least that it is possible to isolate functional Treg that will do their job in vivo. In literature there are very contradictory results regarding functionality of human induced Treg.

Therefore we are also looking more into the functionality of FOXP3 expressing human induced Treg.

Cell culture of T cells and different types of DC, FACS, Elisa, luminex, gel electrophoresis, confocal microscopy, immunohistochemistry, in vivo animal studies

6 or 9 months

Dr. Mark Klein, 088 75 555 55 (pager 4118), mklein01@umcutrecht.nl