Potential Role of γδ T Cell-Derived IL-17 in Acute Cardiac Allograft Rejection

Jichi Medical University, Totigi, Tochigi, Japan
The Annals of thoracic surgery (Impact Factor: 3.85). 05/2012; 94(2):542-8. DOI: 10.1016/j.athoracsur.2012.03.049
Source: PubMed


Although αβ T cells are known to participate in the development of acute cardiac allograft rejection, the role of γδ T cells remains poorly understood. We hypothesized that γδ T cells contribute to acute allograft rejection thru interleukin (IL)-17 production.
Donor hearts from FVB mice (H-2q) were heterotopically transplanted into C57BL/6-wild type (WT) and γδ T cell-deficient (TCRδ-/-) recipient mice (H-2b). Overall graft survival was monitored. Graft infiltrating cell profile, including γδ T cell subtype, cytokine expression, and myeloperoxidase activity were measured by flow cytometry, TaqMan (Applied Biosystems, Carlsbad, CA) polymerase chain reaction, and myeloperoxidase assay, respectively, on postoperative days 3 and 6.
Graft survival was prolonged in TCRδ-/- recipients compared with WT controls. Graft infiltrating cells, including CD45+, CD4+, CD8+, and Gr1+ cells were significantly decreased in TCRδ-/- recipients compared with WT. Donor hearts transplanted into TCRδ-/- recipients had reduced IL-17 and IL-6 messenger RNA expression. Corroborating the gene expression, intracellular cytokine staining showed decreased IL-17 producing cells in TCRδ-/- recipients. Finally, Vγ1+ and Vγ4+ T cells did not produce IL-17, although both represent 20% to 30% total graft infiltrating γδ T cells.
The γδ T cells promote acute cardiac allograft rejection, presumably by producing IL-17. The γδ T cell depletion may prove beneficial in prolonging allograft survival by suppressing IL-17 production.

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    ABSTRACT: BACKGROUND: γδ T cell comprise about 5% of the overall T cell population and they differ from conventional αβ T cells. Previous papers have indicated the contribution of γδ T cell to acute allograft rejection, but the role of γδ T cell in cardiac allograft vasculopathy is not investigated. METHODS: Hearts of adult B6.C-H-2(bm12) KhEg were heterotopically transplanted into major histocompatibility complex (MHC) class‖-mismatched C57BL/6 mice (wild-type, γδ TCR(-/-) ), which is an established murine model of chronic allograft rejection without immunosuppression. The survival of grafts was monitored daily by abdominal palpation until the complete cessation of cardiac contractility. RESULTS: Our current study demonstrated that γδ TCR deficiency significantly attenuated cardiac allograft vasculopathy, and this effect coincide with low expression of Hmgb1, IFN-γ and IL-17 while increased number of CD4(+) CD25(+) Foxp3(+) regulatory T cells, and depletion of regulatory T cells abrogated the prolonged allograft survival induced by γδ TCR deficiency. CONCLUSIONS: γδ TCR deficiency resulted in attenuated cardiac allograft vasculopathy and prolonged graft survival in murine models of cardiac transplantation, and this effect was associated with enhanced expansion of regulatory T cells. This article is protected by copyright. All rights reserved.
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