Critical roles for IL-4, IL-5, and eosinophils in chronic skin allograft rejection
Alain Le Moine, … , Michel Goldman, Daniel Abramowicz
Alain Le Moine, … , Michel Goldman, Daniel Abramowicz
Published June 15, 1999
Citation Information: J Clin Invest. 1999;103(12):1659-1667. https://doi.org/10.1172/JCI5504.
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Article

Critical roles for IL-4, IL-5, and eosinophils in chronic skin allograft rejection

Abstract

C57BL/6 mice injected with the 145-2C11 anti-CD3 mAb and grafted with MHC class II disparate bm12 skin develop a chronic rejection characterized by interstitial dermal fibrosis, a marked eosinophil infiltrate, and an obliterative intimal vasculopathy. Because these changes occur in the absence of alloreactive antibodies, we examined the contribution of cytokines in their pathogenesis. Chronically rejected grafts showed a marked accumulation of both IL-4 and IL-5 mRNA. Mixed lymphocyte reaction experiments established that mice undergoing chronic rejection were primed for IL-4, IL-5, and IL-10 secretion. In vivo administration of anti–IL-4 mAb completely prevented allograft vasculopathy as well as graft eosinophil infiltration and dermal fibrosis. Injection of anti–IL-5 mAb or the use of IL-5–deficient mice as recipients also resulted in the lack of eosinophil infiltration or dermal fibrosis, but these mice did develop allograft vasculopathy. Administration of anti–IL-10 mAb did not influence any histologic parameter of chronic rejection. Thus, in this model, IL-4– and IL-5–mediated tissue allograft eosinophil infiltration is associated with interstitial fibrosis. IL-4, but not eosinophils, is also required for the development of obliterative graft arteriolopathy.

Authors

Alain Le Moine, Véronique Flamand, François-Xavier Demoor, Jean-Christophe Noël, Murielle Surquin, Robert Kiss, Marie-Anne Nahori, Marina Pretolani, Michel Goldman, Daniel Abramowicz

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Allograft eosinophil infiltrate: effect of anti–IL-4 and anti–IL-5 mAb a...
Allograft eosinophil infiltrate: effect of anti–IL-4 and anti–IL-5 mAb administration. (a) Syngeneic skin graft 40 days after transplantation. The dermis, below the epidermal layer (E), is free of inflammatory cells. Sebaceous glands (S) and hair follicles (H) show a normal appearance (hematoxylin and eosin, ×200). (b) bm12 skin allografts at day 40 from a mouse that received anti-CD3 and the control mAb. There is a massive infiltration of the dermis by leukocytes. Up to 35% of the infiltrating leukocytes were identified as eosinophils (refer to c). The number of sebaceous glands and hair follicles is reduced, and those remaining are being engulfed by inflammatory cells (arrow) (hematoxylin and eosin, ×100). (c) bm12 skin allografts at day 40 from a mouse that received anti-CD3 and the control mAb. The dermis is heavily infiltrated by eosinophils, recognizable by the red spots in the cytoplasm (arrows) (hematoxylin and eosin, ×1,000). (d) bm12 skin allografts at day 40 from a mouse that received anti-CD3 and the control mAb. A shrinking hair follicle is being infiltrated by numerous eosinophils (arrows) (hematoxylin and eosin, ×400). (e) bm12 skin allografts at day 40 from a mouse that received anti-CD3 and anti–IL-4 mAb. The aspect is similar to that of a syngeneic graft. The dermis is free of eosinophils. (f) bm12 skin allografts at day 40 from a mouse that received anti-CD3 and anti–IL-5 mAb. There is only a small number of leukocytes present in the dermis. The structure of hair follicles (H) and sebaceous glands (S) are well preserved (compare with b) (hematoxylin and eosin, ×200).