@phdthesis{Jonas2021,
  author    = {Jonas, Franziska},
  title     = {CNS1-dependency of \(in\) \(vivo\) peptide-induced CD4\(^+\)Foxp3\(^+\) regulatory T cells},
  doi       = {10.25972/OPUS-24388},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-243887},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {CD4+Foxp3+ Tregs can be induced in vitro by TGF-b stimulation. Here, CNS1 deficient CD4+ T cells were found to show compromised Foxp3 upregulation in vitro compared to CNS1 WT CD4+ T cells. Moreover, we could demonstrate that antigen-specific CD4+Foxp3+ Tregs can be induced in vivo by tolerogenic antigen stimulation. Parenteral application of agonist BDC2.5 mimetope induced Foxp3 expression in CD4+ BDC2.5 tg cells. We could show that induction of Foxp3 expression by tolerogenic peptide stimulation is impaired in CNS1 deficient CD4+ BDC2.5 tg cells compared to CNS1 WT CD4+ BDC2.5 tg controls. These results indeed indicate that in vivo induced Tregs share mechanistic characteristics with naturally occurring pTregs. Additional in vivo experiments with blocking monoclonal anti-TGF-b demonstrated that high dosage TGF-b blockade abrogated peptide-induced Foxp3 expression in CNS1 WT BDC2.5 tg CD4+ cells, akin to what is seen for impaired Foxp3 upregulation in peptide-stimulated CNS1 KO BDC2.5 tg CD4+ cells without anti-TGF-b-treatment. Adoptive transfer of CD4+CD25- T cells in T cell deficient recipients dramatically increased CD4+Foxp3+ Treg frequencies in both CNS1 WT CD4+ and CNS1 KO CD4+ donor cells. Despite an initially lower increase in Foxp3 expression in CNS1 KO donor cells compared to CNS1 WT donor cells early after transfer, in this setting impaired Treg induction in CNS1 deficient cells was not preserved over time. Consequently, diabetes onset and progression were indistinguishable between mice that received CNS1 WT or CNS1 KO donor cells. Additional Foxp3 induction by peptide stimulation of immunodeficient recipients after transfer of CNS1 WT BDC2.5. tg or CNS1 KO BDC2.5 tg donor cells was not detectable.},
  subject      = {Regulatorischer T-Lymphozyt},
  language  = {en}
}