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Rhoh deficiency reduces peripheral T-cell function and attenuates allogenic transplant rejection

Rhoh is a hematopoietic system-specific GTPase. Rhoh-deficient T cells have been shown to have a defect in TCR signaling manifested during their thymic development. Our aims were to investigate the phenotype of peripheral Rhoh-deficient T cells and to explore in vivo the potential benefit of Rhoh de...

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Main Authors: Porubský, Štefan (Author) , Wang, Shijun (Author) , Kiss, Eva (Author) , Dehmel, Stefan (Author) , Bonrouhi, Mahnaz (Author) , Dorn, Tatjana (Author) , Luckow, Bruno (Author) , Brakebusch, Cord (Author) , Gröne, Hermann-Josef (Author)
Format: Article (Journal)
Language:English
Published: 2011
In: European journal of immunology
Year: 2011, Volume: 41, Issue: 1, Pages: 76-88
ISSN:1521-4141
DOI:10.1002/eji.201040420
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/eji.201040420
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Author Notes:Stefan Porubsky, Shijun Wang, Eva Kiss, Stefan Dehmel, Mahnaz Bonrouhi, Tatjana Dorn, Bruno Luckow, Cord Brakebusch and Hermann-Josef Gröne
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Summary:Rhoh is a hematopoietic system-specific GTPase. Rhoh-deficient T cells have been shown to have a defect in TCR signaling manifested during their thymic development. Our aims were to investigate the phenotype of peripheral Rhoh-deficient T cells and to explore in vivo the potential benefit of Rhoh deficiency in a clinically relevant situation, in which T-cell inhibition is desirable. In murine allogenic kidney transplantation, Rhoh deficiency caused a significant 75% reduction of acute and chronic transplant rejection accompanied by 75% lower alloantigen-specific antibody levels and significantly better graft function. This effect was independent of the lower T-cell numbers in Rhoh-deficient recipients, because injection of equal numbers of Rhoh-deficient or control T cells into kidney transplanted mice with SCID led again to a significant 60% reduction of rejection. Mixed lymphocyte reaction revealed that the weaker alloreactivity was associated with a 85% lower cytotoxicity and a 50-80% lower cytokine release in Rhoh-deficient T cells without an influence on the secretion itself. Antigen uptake and presentation in DC were unaffected by Rhoh deficiency. These findings stress the importance of Rhoh for the function of peripheral T cells.
Item Description:First published: 13 October 2010
Gesehen am 12.01.2023
Physical Description:Online Resource
ISSN:1521-4141
DOI:10.1002/eji.201040420

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