Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Fechter, K; Dorronsoro, A; Jakobsson, E; Ferrin, I; Lang, V; Sepulveda, P; Pennington, DJ; Trigueros, C.
IFNγ Regulates Activated Vδ2+ T Cells through a Feedback Mechanism Mediated by Mesenchymal Stem Cells.
PLoS One. 2017; 12(1): e0169362-e0169362.
Doi: 10.1371/journal.pone.0169362
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- Leading authors Med Uni Graz
- Fechter Karoline
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- Abstract:
- γδ T cells play a role in a wide range of diseases such as autoimmunity and cancer. The majority of circulating human γδ T lymphocytes express a Vγ9Vδ2+ (Vδ2+) T cell receptor (TCR) and following activation release pro-inflammatory cytokines. In this study, we show that IFNγ, produced by Vδ2+ cells, activates mesenchymal stem cell (MSC)-mediated immunosupression, which in turn exerts a negative feedback mechanism on γδ T cell function ranging from cytokine production to proliferation. Importantly, this modulatory effect is limited to a short period of time (<24 hours) post-T cell activation, after which MSCs can no longer exert their immunoregulatory capacity. Using genetically modified MSCs with the IFNγ receptor 1 constitutively silenced, we demonstrate that IFNγ is essential to this process. Activated γδ T cells induce expression of several factors by MSCs that participate in the depletion of amino acids. In particular, we show that indolamine 2,3-dioxygenase (IDO), an enzyme involved in L-tryptophan degradation, is responsible for MSC-mediated immunosuppression of Vδ2+ T cells. Thus, our data demonstrate that γδ T cell responses can be immuno-modulated by different signals derived from MSC.
- Find related publications in this database (using NLM MeSH Indexing)
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- Immune Tolerance - drug effects
- Interferon-gamma - pharmacology
- Lymphocyte Activation - drug effects
- Mesenchymal Stromal Cells - drug effects
- Mesenchymal Stromal Cells - physiology
- Receptors, Antigen, T-Cell, gamma-delta - metabolism
- Signal Transduction - drug effects
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