title: Monokine induced by interferon-gamma (MIG/CXCL9) is derived from both donor and recipient sources during rejection of class II major histocompatibility complex disparate skin allografts.
abstract: Chemokines, including monokine induced by interferon-gamma (Mig/CXCL9), are produced both in allografts and during the direct T-cell infiltration that mediates graft rejection. Neither the specific production nor contribution of allograft donor versus recipient Mig in allograft rejection is currently known. C57BL/6 mice with a targeted deletion in the Mig gene were used as both skin allograft donors and recipients in a class II major histocompatibility complex-mismatched graft model to test the requirement for donor- versus recipient-derived Mig for acute rejection. B6.Mig(-/-) allografts had a 10-day prolonged survival in B6.H-2(bm12) recipients when compared with wild-type C57BL/6 allograft donors, and B6.H-2(bm12) skin allografts had a 5-day prolonged survival in B6.Mig(-/-) versus wild-type recipients. Transplantation of B6.Mig(-/-) skin grafts onto B6.H-2(bm12).Mig(-/-) recipients resulted in further prolonged allograft survival with more than 30% of the grafts surviving longer than 60 days. Prolonged allograft survival was also associated with delayed cellular infiltration into grafts but not with altered T-cell proliferative responses to donor stimulators. Immunohistochemical staining of allograft sections indicated that Mig is produced by both donor- and recipient-derived sources, but Mig from each of these sources appeared in different areas of the allograft tissue. These results therefore demonstrate the synergy of donor- and recipient-derived Mig in promoting T-cell infiltration into allografts.
authors.affiliation: NB3-59, Department of Immunology, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195-0001, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Auerbach
authors.forename: Naohiko
authors.initials: N
authors.lastname: Shimoda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Amano
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Rosenblum
authors.forename: Danielle D
authors.initials: DD
authors.lastname: Kish
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Farber
authors.forename: Robert L
authors.initials: RL
authors.lastname: Fairchild
mesh_terms: D000818:Animals; D054370:Chemokine CXCL9 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015846:Monokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology*
chemical_list: D054370:Chemokine CXCL9; D000949:Histocompatibility Antigens Class II; D015846:Monokines; D007371:Interferon-gamma