IL-5 mediates eosinophilic rejection of MHC class II-disparate skin allografts in mice

CD4 T cells play a crucial role in the acute rejection of MHC class II-disp arate skin allografts, mainly by Fas/Fas ligand-mediated cytotoxicity. Beca use recent observations indicate that eosinophils may be found within allog rafts rejected by CD4 T cells, we evaluated the role played by IL-5, the ma in eosinophil growth factor, and by eosinophils in the rejection of MHC cla ss II-disparate skin grafts, C57BL/6 mice rapidly rejected MHC class II-dis parate bm12 skin grafts. Rejected skins contained a dense, aggressive eosin ophil infiltrate. Lymphocytes isolated from lymph nodes draining rejected b m12 skin were primed for IL-5 secretion, and IL-5 mRNA was present within r ejected grafts. The IL-5/eosinophil pathway played an effector role in allo graft destruction, because the rejection of bm12 skin was significantly del ayed 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-dispa rate donor-recipient strains unable to establish Fas/Fas ligand interaction s. Fas ligand-deficient gld/gld mice rejected bm12 skins, and bm12 mice rej ected Fas-deficient lpr/lpr C57BL/6 skins, Neutralization of IL-5 prevented acute rejection in both combinations. We conclude that MHC class II-dispar ate skin allografts trigger an IL-5-dependent infiltration of eosinophils t hat is sufficient to result in acute graft destruction.