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PLoS One. 2017 Jan 11;12(1):e0169362. doi: 10.1371/journal.pone.0169362. eCollection 2017.

IFNγ Regulates Activated Vδ2+ T Cells through a Feedback Mechanism Mediated by Mesenchymal Stem Cells.

Author information

1
Fundación Inbiomed, Foundation for Stem Cell Research, Mesenchymal Stem Cell Laboratory, Paseo Mikeletegi, San Sebastián, Spain.
2
Fundación para la Investigación Hospital Universitario La Fe, Valencia, Spain.
3
Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom.

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.

PMID:
28076364
PMCID:
PMC5226805
DOI:
10.1371/journal.pone.0169362
[Indexed for MEDLINE]
Free PMC Article

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