T cell infiltration into class II MHC-disparate allografts and acute rejection is dependent on the IFN-gamma-induced chemokine Mig

Direct evidence that cytokines with chemoattractant properties for leukocyt es, chemokines, recruit alloantigen-primed T cells into transplanted allogr afts has been lacking, We present evidence that neutralization of a single chemokine inhibits T cell infiltration into class II MHC-disparate murine a llografts and acute rejection. The chemokines IFN-gamma-inducible protein-1 0 and monokine induced by IFN-gamma (Mig) are expressed in allogeneic skin grafts during the late stages of acute rejection, Survival of class II MHC- disparate B6.H-2(bm12) allografts is prolonged from day 14 to day 55 posttr ansplant when C57BL/6 recipients are given a short course treatment with an antiserum to Mig. This treatment also inhibits T cell and macrophage infil tration into the allografts, B6.H-2(bm12) allografts are also not rejected by IFN-gamma(-/-) C57BL/6 recipients. Injection of Mig directly into B6.H-2 (bm12) grafts on IFN-gamma-deficient recipients restores T cell infiltratio n and rejection. Therefore, the inability of IFN-gamma-deficient recipients to reject the class II MHC-disparate allografts is due to the lack of intr aallograft Mig production and alloantigen-primed T cell recruitment to the graft, These results indicate for the first time the potential utility of c hemokine neutralization strategies in preventing T cell infiltration into a llografts and abrogating acute rejection.