Potential Role of γδ T Cell-Derived IL-17 in Acute Cardiac Allograft Rejection
Potential Role of γδ T Cell-Derived IL-17 in Acute Cardiac Allograft Rejection
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DOI：
10.1016/j.athoracsur.2012.03.049
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发表时间：
2012-08-01
影响因子：
4.6
通讯作者：
Fischbein, Michael P.
中科院分区：
文献类型：
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作者：
Kimura, Naoyuki;Nakae, Susumu;Fischbein, Michael P.
背景尽管已知α β T细胞参与急性心脏同种异体移植排斥反应的发生，但对γ δ T细胞的作用仍然知之甚少。我们假设γ δ T细胞通过产生白细胞介素（IL）-17而促进急性同种异体移植排斥反应。将来自FVB小鼠（H-2（q））的供体心脏异位移植到C57 BL/6-野生型（WT）和γ δ T细胞缺陷型（TCR δ（-/-））受体小鼠（H-2（B））中。监测移植物的总体存活率。术后第3天和第6天分别用流式细胞术、TaqMan（Applied Biosystems，卡尔斯巴德，CA）聚合酶链反应和髓过氧化物酶测定法检测移植物浸润细胞的特征，包括γ δ T细胞亚型、细胞因子表达和髓过氧化物酶活性。与WT对照组相比，TCR δ（-/-）受体移植物存活时间延长。与WT相比，TCR δ（-/-）受体的移植物浸润细胞，包括CD 45（+）、CD 4（+）、CD 8（+）和Gr 1（+）细胞显著减少。移植到TCR δ（-/-）受体的供体心脏具有降低的IL-17和IL-6信使RNA表达。细胞内细胞因子染色证实了基因表达，显示TCR δ（-/-）受体中IL-17产生细胞减少。最后，V γ 1（+）和V γ 4（+）T细胞不产生IL-17，尽管两者均占总移植物浸润γ δ T细胞的20%至30%。γ δ T细胞可能通过产生IL-17促进急性心脏同种异体移植排斥反应。γ δ T细胞耗竭可能通过抑制IL-17的产生而有益于延长同种异体移植物的存活。(Ann Thorac Surg 2012;94：542-8）（c）2012年，胸外科医师协会
Background. Although alpha beta T cells are known to participate in the development of acute cardiac allograft rejection, the role of gamma delta T cells remains poorly understood. We hypothesized that gamma delta T cells contribute to acute allograft rejection thru interleukin (IL)-17 production.Methods. Donor hearts from FVB mice (H-2(q)) were heterotopically transplanted into C57BL/6-wild type (WT) and gamma delta T cell-deficient (TCR delta(-/-)) recipient mice (H-2(b)). Overall graft survival was monitored. Graft infiltrating cell profile, including gamma delta 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.Results. Graft survival was prolonged in TCR delta(-/-) recipients compared with WT controls. Graft infiltrating cells, including CD45(+), CD4(+), CD8(+), and Gr1(+) cells were significantly decreased in TCR delta(-/-) recipients compared with WT. Donor hearts transplanted into TCR delta(-/-) 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 TCR delta(-/-) recipients. Finally, V gamma 1(+) and V gamma 4(+) T cells did not produce IL-17, although both represent 20% to 30% total graft infiltrating gamma delta T cells.Conclusions. The gamma delta T cells promote acute cardiac allograft rejection, presumably by producing IL-17. The gamma delta T cell depletion may prove beneficial in prolonging allograft survival by suppressing IL-17 production. (Ann Thorac Surg 2012;94:542-8) (c) 2012 by The Society of Thoracic Surgeons