Monokine induced by interferon-γ (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-γ (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-2bm12 recipients when compared with wildtype C57BL/6 allograft donors, and B6.H-2bm12 skin allografts had a 5-day prolonged survival in B6.Mig-/- versus wild-type recipients. Transplantation of B6.Mig-/- skin grafts onto B6.H-2bm12.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 recipientderived Mig in promoting T-cell infiltration into allografts. Copyright © American Society for Investigative Pathology.