[Blockade of B7:CD28 costimulatory pathway reduces the vascular damage in an experimental model of chronic rejection].
OBJECTIVE
Costimulatory blockade and donor specific transfusion (DST) can catalyze tolerance of transplanted organs through a multistep adaptation between the recipient and donor immune systems. Such an in vivo process may prolong graft survival. Aim of this study was to evaluate the outcome of aortic transplantation under CTLA4Ig and DST in a mismatched model in rats.


METHODS
Orthotopic aortic transplantation was performed in recipients Lewis from Wistar-Furth rats. The animals were stratified into 3 groups, according to the postoperative treatment. Group 1 had aortic transplantation only (controls, n=6), while group 2 (n=7) had a load of donor splenocytes (DST). Group 3 was treated with DST and CTLA4Ig. All the animals were sacrificed at the 60th postoperative day and the aortic specimens were prepared for histology. Intimal cells, muscular cells and lymphocyte cell infiltration were evaluated by serial counts.


RESULTS
In Group 1 there was a severe chronic rejection, while group 2 showed a slower onset of chronic rejection with less inflammatory infiltrate than group 1 (P<0.05). Group 3 had the best overall outcome with lower infiltration and minimal alterations compared with groups 1 and 2.


CONCLUSIONS
Costimulatory blockade and DST load can prevent the onset of chronic rejection in this experimental setting. Despite the wide availability of immunosuppressors, which makes transplantation a today's clinical routine, the solution to chronic rejection is still elusive. The synergistic role of splenocytes and costimulatory blockade raises interesting perspectives about the immunomodulatory role of spleen in tolerance induction.
Rademacher
J
J
Laboratorio di Chirurgia Sperimentale, Sezione di Chirurgia Generale, Dipartimento di Chirurgia, Università degli Studi di Pavia, Pavia.
Cansolino
L
L
Lillo
E
E
Oldani
G
G
Delfino
A
A
Matteotti
C
C
Gaspari
A
A
Maestri
M
M
Dionigi
P
P
D000818:Animals; D001011:Aorta / Q000276:immunology* / Q000473:pathology / Q000637:transplantation / Q000648:ultrastructure; D018122:B7-1 Antigen / Q000276:immunology*; D001808:Blood Vessels / Q000187:drug effects*; D018106:CD28 Antigens / Q000276:immunology*; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D018796:Immunoconjugates / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014184:Transplantation, Homologous
D018122:B7-1 Antigen; D018106:CD28 Antigens; D018796:Immunoconjugates