Early chemokine cascades in murine cardiac grafts regulate T cell recruitment and progression of acute allograft rejection

The identification of early inflammatory events after transplant in solid t issue organ grafts that may direct T cell recruitment and promote acute all ograft rejection remain largely unknown. To better understand temporal aspe cts of early inflammatory events in vascularized organ grafts, we tested th e intragraft expression of four different chemokines in heterotopically tra nsplanted Ad (H-2(n)) and syngeneic heart grafts in C57BL/6 (H-2(b)) recipi ent mice from 1.5 to 48 h after transplant. Similar temporal expression pat terns and equivalent levels of chemokine expression were observed in both s yngeneic and allogeneic cardiac allografts during this time period. Express ion of the neutrophil chemoattractant growth-related oncogene ce (KC) was o bserved first and reached peak levels by 6 h after transplant and was follo wed by the monocyte/macrophage chemoattractant protein-1 (JE) and then macr ophage inflammatory proteins 1 beta and 1 alpha. Administration of rabbit K C antiserum to allograft recipients within 30 min of cardiac transplantatio n attenuated downstream events including intra-allograft expression of the T cell chemoattractants IFN-gamma -inducible protein-10 and monokine induce d by IFN-gamma, cellular infiltration into the allograft, and graft rejecti on. Similarly, depletion of recipient neutrophils at the time of transplant ation significantly extended allograft survival from day 8 to 10 in control -treated recipients up to day 21 after transplant. These results indicate t he induction of highly organized cascades of neutrophil and macrophage chem oattractants in cardiac grafts and support the proposal that early inflamma tory events are required for optimal recruitment of T cells into allografts during the progression of acute rejection of cardiac allografts.