RANTES CHEMOKINE EXPRESSION IS RELATED TO ACUTE CARDIAC CELLULAR REJECTION AND INFILTRATION BY CD45RO T-LYMPHOCYTES AND MACROPHAGES

Background: Despite the advances made in immunosuppression therapy, ep isodes of acute cellular rejection may affect graft function and survi val. We investigated the role of RANTES in cellular recruitment and in cardiac allograft rejection. Methods: Endomyocardial biopsies (n = 65 ) from 30 patients were taken at various times after transplantation. Ln 4 subjects who died of acute cellular rejection, the profile of RAN TES expression was monitored in all biopsy specimens and in postmortem tissue. Myocardial tissue from 10 other transplants was also analyzed . Sections were stained with an anti-human RANTES antibody with the st reptavidin-biotin technique. RANTES-positive cells were related to mac rophage, CD45RO ''memory'' T-cell, and eosinophil infiltration. Result s: RANTES-positive cells were identified within the cellular infiltrat e in 95% of biopsies with moderate/severe rejection and 28% with mild rejection. RANTES-positive, CD45RO-positive, and macrophage cell numbe rs were higher in subjects who died of acute cellular rejection than o f other causes. A highly significant difference in RANTES-positive cel l number was observed between moderate/severe, mild, and nonrejection groups (p = .0001) and correlated significantly with macrophage number in both right and left ventricles (r = .693, p < .01; r = .599, p < . 05, respectively) and with the number of ''memory'' T cells (r = .829, p < .001; r = .779, p < .01, respectively). Conclusions: These findin gs suggest that local release of RANTES is important in the recruitmen t of both macrophages and CD45RO T cells in cardiac allograft rejectio n. RANTES may be an important chemokine to target for therapeutic inte rvention in heart rejection.