T. Misao et al., EFFICACY OF COMBINING DONOR-SPECIFIC PRESENSITIZATION WITH A SIMULTANEOUS SINGLE INJECTION OF TACROLIMUS ON PULMONARY ALLOGRAFTS, The Journal of heart and lung transplantation, 16(11), 1997, pp. 1099-1105
Background: We investigated the effects of combining donor-specific pr
esensitization with a simultaneous injection of tacrolimus by use of a
fully allogeneic rat lung allograft model. Methods: Lungs from Brown
Norway donor rats were orthotopically transplanted into Lewis recipien
t rats. Seven days before transplantation, allograft recipients receiv
ed a transfusion of donor splenocytes (1 x 10(8) cells, intravenously)
, tacrolimus (3 or 1.5 mg/ kg, intramuscularly), or a combination. No
posttransplantation immunosuppression was given. In the transplantatio
n study, graft survival was evaluated, and histologic characteristics
of acute rejection were graded. In the in vitro studies, mixed lymphoc
yte reaction assays were used to investigate the effects of pretreatme
nt on immune response. Results: The graft survival evaluation disclose
d that untreated rats rejected the allografts at 4.6 +/- 0.2 days. Don
or splenocyte transfusion alone accelerated the graft rejection (3.3 /- 0.2 days). Tacrolimus (3 mg/kg) alone moderately improved the graft
survival (8.7 +/- 0.6 days). When donor splenocyte transfusion was co
mbined with tacrolimus, graft survival was significantly increased to
29.6 +/- 12.0 days. In a mixed lymphocyte reaction assay, peripheral b
lood lymphocytes obtained from animals pretreated with donor splenocyt
e transfusion alone seemed to be hyperresponsive against the donor lym
phocytes. In contrast, donor splenocyte transfusion with tacrolimus si
gnificantly suppressed the proliferative response against the donor ly
mphocytes but not against third-party lymphocytes obtained from naive
Wistar King A rats. Conclusion: These data demonstrate that donor-spec
ific presensitization with a simultaneous single injection of tacrolim
us prevented both sensitization and graft rejection and induced donor-
specific unresponsiveness. J Heart Lung Transplant 1997.