BACKGROUND: Donor-specific tolerance to heart allografts in the rat can be achieved by donor-specific blood transfusions (DST) before transplantation. This tolerance induction requires the presence of host CD8 T cells and is characterized by the infiltration of numerous leukocytes. METHODS: To identify new mediators involved in tolerance induction, gene searching was performed and resulted in the identification of the Fractalkine receptor, CX3CR1, as being highly expressed in tolerated allografts. RESULTS: We showed that the high CX3CR1 mRNA accumulation found in tolerated allografts was related to the active recruitment of monocytes/macrophages. CX3CR1 transcript accumulation was preceded by an early expression of its ligand, Fractalkine, by graft endothelial cells. Interestingly, depletion of recipient CD8 cells led to a dramatic decrease in both CX3CR1 and Fractalkine mRNA levels. Moreover, in vitro, CD8 T cells from DST-primed animals were found to strongly induce Fractalkine expression in an allogeneic endothelial cell line. CONCLUSION: This is the first report describing Fractalkine, a chemokine usually described in inflammatory processes, as being expressed in a model of allograft tolerance.
BACKGROUND:Donor-specific tolerance to heart allografts in the rat can be achieved by donor-specific blood transfusions (DST) before transplantation. This tolerance induction requires the presence of host CD8 T cells and is characterized by the infiltration of numerous leukocytes. METHODS: To identify new mediators involved in tolerance induction, gene searching was performed and resulted in the identification of the Fractalkine receptor, CX3CR1, as being highly expressed in tolerated allografts. RESULTS: We showed that the high CX3CR1 mRNA accumulation found in tolerated allografts was related to the active recruitment of monocytes/macrophages. CX3CR1 transcript accumulation was preceded by an early expression of its ligand, Fractalkine, by graft endothelial cells. Interestingly, depletion of recipient CD8 cells led to a dramatic decrease in both CX3CR1 and Fractalkine mRNA levels. Moreover, in vitro, CD8 T cells from DST-primed animals were found to strongly induce Fractalkine expression in an allogeneic endothelial cell line. CONCLUSION: This is the first report describing Fractalkine, a chemokine usually described in inflammatory processes, as being expressed in a model of allograft tolerance.