Poulin Lionel F, Richard Mélisande, Le Moine Alain, Kiss Robert, McKenzie Andrew N, Goldman Michel, Renauld Jean-Christophe, Van Snick Jacques, Braun Michel Y
The Laboratory of Experimental Immunology, Université Libre de Bruxelles, 808 route de Lennik, 1070 Brussels, Belgium.
Transplantation. 2003 Aug 15;76(3):572-7. doi: 10.1097/01.TP.0000071201.32424.D2.
Eosinophils participate in allograft rejection when donor-reactive helper T lymphocytes are T-helper type 2 (Th2)-biased. Whereas the involvement of interleukin (IL)-4 and IL-5 in these forms of rejection is well established, the role of IL-9, another Th2-type cytokine promoting eosinophilia, has not been determined.
We first used real-time polymerase chain reaction to quantify IL-9 mRNA in rejected allografts in a mouse model of fully mismatched heart transplantation in which recipients were devoid of CD8 T cells and developed a Th2 alloimmune response. We then compared allograft survival in wild-type versus IL-9-deficient mice depleted of CD8 T cells. Finally, we compared the fate of major histocompatibility complex class II-mismatched cardiac transplants from wild-type versus IL-9 transgenic donors to determine the influence of IL-9 overexpression within the graft.
The Th2 alloimmune response in CD8-deficient mice was associated with the accumulation of IL-9 mRNA in the rejected graft. In IL-9-deficient recipients depleted of CD8 T cells, eosinophil infiltration of heart allografts did not develop, but rejection still occurred. In the major histocompatibility complex class II disparate model, heart allografts from IL-9 transgenic donors were acutely rejected, whereas grafts from wild-type donors did not develop rejection. Acute rejection of IL-9 transgenic hearts was associated with massive eosinophil infiltration and prevented by neutralization of either IL-4 or IL-5.
IL-9 is critically involved in heart transplant eosinophilia in conjunction with IL-4 and IL-5.
当供体反应性辅助性T淋巴细胞偏向2型辅助性T细胞（Th2）时，嗜酸性粒细胞参与同种异体移植排斥反应。虽然白细胞介素（IL）-4和IL-5在这些排斥反应形式中的作用已得到充分证实，但另一种促进嗜酸性粒细胞增多的Th2型细胞因子IL-9的作用尚未确定。
我们首先使用实时聚合酶链反应来定量在完全不匹配心脏移植小鼠模型中被排斥的同种异体移植物中的IL-9 mRNA，在该模型中受体缺乏CD8 T细胞并产生Th2同种免疫反应。然后我们比较了野生型小鼠与缺乏IL-9且CD8 T细胞耗竭的小鼠的同种异体移植物存活率。最后，我们比较了来自野生型与IL-9转基因供体的主要组织相容性复合体II类不匹配心脏移植的转归，以确定移植物中IL-9过表达的影响。
CD8缺陷小鼠中的Th2同种免疫反应与被排斥移植物中IL-9 mRNA的积累有关。在缺乏IL-9且CD8 T细胞耗竭的受体中，心脏同种异体移植物没有出现嗜酸性粒细胞浸润，但排斥反应仍然发生。在主要组织相容性复合体II类不同模型中，来自IL-9转基因供体的心脏同种异体移植物被急性排斥，而来自野生型供体的移植物没有发生排斥反应。IL-9转基因心脏的急性排斥反应与大量嗜酸性粒细胞浸润有关，并且通过中和IL-4或IL-5可以预防。
IL-9与IL-4和IL-5一起在心脏移植嗜酸性粒细胞增多中起关键作用。
