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Thesis (Master's)

University of Iceland > Heilbrigðisvísindasvið > Meistaraprófsritgerðir - Heilbrigðisvísindasvið >

Please use this identifier to cite or link to this item: http://hdl.handle.net/1946/15173

Title: 
  • Effects of pro-inflammatory cytokines on iTReg differentiation and function
  • Title is in Icelandic Áhrif bólgumiðlandi boðefna á sérhæfingu og virkni T stýrifrumna
Degree: 
  • Master's
Abstract: 
  • Regulatory CD4+ T cells (TRegs) are one of the key elements of peripheral tolerance and suppression of autoimmune diseases. They are divided into two classes; central natural TRegs (nTRegs) and peripherally induced TRegs (iTRegs) which are phenotypically indistinguishable but differ regarding their differentiation and function. nTRegs develop in the thymus but iTRegs require the presence of IL-2 and TGF-β to be induced. They are thought to have a suppressive function but their mechanism of suppression is unknown. It has been revealed that the innate immune system plays a significant role in the immunopathology of autoimmunity. However, its part in differentiation and function of human CD4+ iTRegs is still unclear.
    The aim of this study was to evaluate the role of pro-inflammatory cytokines of the innate immune response on the differentiation and function of human induced TRegs.
    All experiments were conducted on human T cells isolated from adult peripheral blood. Naïve T cells (CD4+CD25-) were isolated and stimulated with anti-CD3 and cultured in the presence of IL-2 and TGF-β with or without the pro-inflammatory cytokines IL-1β and TNFα for five days. The phenotype of iTRegs was defined as CD4+CD127-CD25highFoxP3high and they were analysed with flow cytometry. To detect their capacity to suppress PBMC’s proliferation, iTRegs were co-cultured with CFSE labelled PBMC’s and Epstein-Barr infected B cells pulsed with superantigens.
    We found that the highest fraction of ex vivo differentiated CD4+ iTRegs was dependent on the presence of both IL-2 and TGF-β1. The pro-inflammatory cytokines IL-1β and TNFα were also demonstrated to significantly inhibit TGF-β1 induced TReg differentiation in vitro. The TGF-β induced TRegs showed strong suppressive function ex vivo and their suppressive function correlated positively with their numbers in culture. This suppressive capacity of the iTRegs was contained in the presence of IL-1β and TNFα. Our results showed that the iTRegs did not mediate their suppression through secretion of IL-10 or IL-36 but possibly through IL-2 secretion.

Sponsor: 
  • Sponsor is in Icelandic Vísindasjóður LSH
Accepted: 
  • May 22, 2013
URI: 
  • http://hdl.handle.net/1946/15173


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