Induction of Fractalkine and CX3CR1 mediated by host CD8+ T cells in allograft tolerance induced by donor specific blood transfusion.
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.


CONCLUSIONS
This is the first report describing Fractalkine, a chemokine usually described in inflammatory processes, as being expressed in a model of allograft tolerance.
Louvet
Cédric
C
INSERM Unité 643 (ex 437) Immunointervention dans les allo- et xeno-transplantations, Institut de Transplantation et de Recherche en Transplantation (ITERT), Nantes, France.
Heslan
Jean-Marie
JM
Merieau
Emmanuel
E
Soulillou
Jean-Paul
JP
Cuturi
Maria-Cristina
MC
Chiffoleau
Elise
E
D000818:Animals; D001803:Blood Transfusion; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000096:biosynthesis*; D007108:Immune Tolerance; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D018121:Receptors, Cytokine / Q000096:biosynthesis* / Q000235:genetics; D015728:Receptors, HIV / Q000096:biosynthesis* / Q000235:genetics; D014184:Transplantation, Homologous
D000073883:CX3C Chemokine Receptor 1; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515540:Cx3cl1 protein, rat; D008565:Membrane Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D015728:Receptors, HIV