Le Moine A, Surquin M, Demoor F X, Noël J C, Nahori M A, Pretolani M, Flamand V, Braun M Y, Goldman M, Abramowicz D
Laboratory of Experimental Immunology, Université Libre de Bruxelles, Belgium.
J Immunol. 1999 Oct 1;163(7):3778-84.
CD4 T cells play a crucial role in the acute rejection of MHC class II-disparate skin allografts, mainly by Fas/Fas ligand-mediated cytotoxicity. Because recent observations indicate that eosinophils may be found within allografts rejected by CD4 T cells, we evaluated the role played by IL-5, the main eosinophil growth factor, and by eosinophils in the rejection of MHC class II-disparate skin grafts. C57BL/6 mice rapidly rejected MHC class II-disparate bm12 skin grafts. Rejected skins contained a dense, aggressive eosinophil infiltrate. Lymphocytes isolated from lymph nodes draining rejected bm12 skin were primed for IL-5 secretion, and IL-5 mRNA was present within rejected grafts. The IL-5/eosinophil pathway played an effector role in allograft destruction, because the rejection of bm12 skin was significantly delayed in IL-5-deficient mice as compared with wild-type animals. The role of the IL-5/eosinophil pathway was further investigated in MHC class II-disparate donor-recipient strains unable to establish Fas/Fas ligand interactions. Fas ligand-deficient gld/gld mice rejected bm12 skins, and bm12 mice rejected Fas-deficient lpr/lpr C57BL/6 skins. Neutralization of IL-5 prevented acute rejection in both combinations. We conclude that MHC class II-disparate skin allografts trigger an IL-5-dependent infiltration of eosinophils that is sufficient to result in acute graft destruction.
CD4 T细胞在MHC II类不同的皮肤同种异体移植急性排斥反应中起关键作用，主要通过Fas/Fas配体介导的细胞毒性作用。由于最近的观察表明，在被CD4 T细胞排斥的同种异体移植物中可能发现嗜酸性粒细胞，我们评估了主要嗜酸性粒细胞生长因子IL-5以及嗜酸性粒细胞在MHC II类不同的皮肤移植物排斥反应中所起的作用。C57BL/6小鼠迅速排斥MHC II类不同的bm12皮肤移植物。被排斥的皮肤中有密集、活跃的嗜酸性粒细胞浸润。从引流被排斥的bm12皮肤的淋巴结中分离出的淋巴细胞可被诱导分泌IL-5，且被排斥的移植物中存在IL-5 mRNA。IL-5/嗜酸性粒细胞途径在同种异体移植物破坏中起效应作用，因为与野生型动物相比，IL-5缺陷小鼠中bm12皮肤的排斥反应明显延迟。在无法建立Fas/Fas配体相互作用的MHC II类不同的供体-受体品系中，对IL-5/嗜酸性粒细胞途径的作用进行了进一步研究。Fas配体缺陷的gld/gld小鼠排斥bm12皮肤，而bm12小鼠排斥Fas缺陷的lpr/lpr C57BL/6皮肤。IL-5的中和作用可阻止这两种组合中的急性排斥反应。我们得出结论，MHC II类不同的皮肤同种异体移植引发了依赖IL-5的嗜酸性粒细胞浸润，这足以导致急性移植物破坏。
