title: IL-5 mediates eosinophilic rejection of MHC class II-disparate skin allografts in mice.
abstract: 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.
authors.affiliation: Laboratory of Experimental Immunology, Université Libre de Bruxelles, Belgium. alemoine@ulb.ac.be
authors.forename: A
authors.initials: A
authors.lastname: Le Moine
authors.forename: M
authors.initials: M
authors.lastname: Surquin
authors.forename: F X
authors.initials: FX
authors.lastname: Demoor
authors.forename: J C
authors.initials: JC
authors.lastname: Noël
authors.forename: M A
authors.initials: MA
authors.lastname: Nahori
authors.forename: M
authors.initials: M
authors.lastname: Pretolani
authors.forename: V
authors.initials: V
authors.lastname: Flamand
authors.forename: M Y
authors.initials: MY
authors.lastname: Braun
authors.forename: M
authors.initials: M
authors.lastname: Goldman
authors.forename: D
authors.initials: D
authors.lastname: Abramowicz
mesh_terms: D000208:Acute Disease; D000818:Animals; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D053222:Fas Ligand Protein; D005260:Female; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D007106:Immune Sera / Q000494:pharmacology; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D008024:Ligands; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008817:Mice, Mutant Strains; D012333:RNA, Messenger / Q000096:biosynthesis; D016038:Skin Transplantation / Q000276:immunology* / Q000473:pathology; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D000949:Histocompatibility Antigens Class II; D007106:Immune Sera; D015848:Interleukin-5; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor