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Therapeutic effect of CXCR3-expressing regulatory T cells on liver, lung and intestinal damages in a murine acute GVHD model

Gene Therapy volume 15, pages 171–182 (2008)Cite this article

Abstract

Adoptive transfer of CD4+CD25+ regulatory T cells has been shown to have therapeutic effects in experimental graft-vs-host disease (GVHD) models. Chemokines play an important role in the recruitment of alloreactive donor T cells into target organs during GVHD. In this study, we investigated the effectiveness of targeted delivery of CD4+CD25+ regulatory T cells via a transfected chemokine receptor on reduction of organ damage during acute GVHD. High levels of expression of Th1-associated chemokines (CXCL9, CXCL10 and CXCL11) and their receptor CXCR3 were observed in the liver, lung and intestine of GVHD-induced recipient mice. Recipient mice that had undergone transfer of CD4+CD25+Foxp3+ CXCR3-transfected T cells (CXCR3-Treg cells) showed significant amelioration of GVHD changes in the liver, lung and intestine in comparison with recipient mice that had received CD4+CD25+Foxp3+ T cells (Treg cells) or naturally occurring CD4+CD25+ regulatory T cells. This was due to more pronounced migration of CXCR3-Treg cells and their localization for a longer time in Th1-associated chemokine-expressing organs, resulting in stronger suppressive activity. We succeeded in preparing chemokine receptor-expressing Treg cells and demonstrated their ability to ameliorate disease progression upon accumulation in target organs. This method may provide a new therapeutic approach for organ damage in acute GVHD.

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Acknowledgements

We thank Miho Terada for an excellent technical assistance. This work was supported by a Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Department of Bioregulatory Medicine, Ehime University Graduate School of Medicine, Ehime, Japan

    H Hasegawa, A Inoue, M Kohno, J Lei & M Yasukawa

  2. Department of Pathology, Division of Pathogenomics, Ehime University Graduate School of Medicine, Ehime, Japan

    T Miyazaki & M Nose

  3. Department of Microbiology, Kinki University School of Medicine, Osaka, Japan

    O Yoshie

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  1. H Hasegawa
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Correspondence to H Hasegawa.

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Hasegawa, H., Inoue, A., Kohno, M. et al. Therapeutic effect of CXCR3-expressing regulatory T cells on liver, lung and intestinal damages in a murine acute GVHD model. Gene Ther 15, 171–182 (2008). https://doi.org/10.1038/sj.gt.3303051

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