Initial in vivo experience of pig artery patch transplantation in baboons using mutant MHC (CIITA-DN) pigs.
Initial in vivo experience of pig artery patch transplantation in baboons using mutant MHC (CIITA-DN) pigs.
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DOI:
10.1016/j.trim.2015.02.003
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发表时间:
2015-03
影响因子:
1.5
通讯作者:
Cooper DK
中科院分区:
文献类型:
--
作者:
Iwase H;Ekser B;Satyananda V;Zhou H;Hara H;Bajona P;Wijkstrom M;Bhama JK;Long C;Veroux M;Wang Y;Dai Y;Phelps C;Ayares D;Ezzelarab MB;Cooper DK
In the pig-to-nonimmunosuppressed baboon artery patch model, a graft from an α1,3-galactosyltransferase gene-knockout pig transgenic for human CD46 (GTKO/CD46) induces a significant adaptive immune response (elicited anti-pig antibody response, increase in T cell proliferation on MLR, cellular infiltration of the graft), which is effectively prevented by anti-CD154mAb-based therapy. As anti-CD154mAb is currently not clinically applicable, we evaluated whether it could be replaced by CD28/B7 pathway blockade or by blockade of both pathways (using belatacept+anti-CD40mAb [2C10R4]). We further investigated whether a patch from a GTKO/CD46 pig with a mutant human MHC class II transactivator (CIITA-DN) gene would allow reduction in the immunosuppressive therapy administered. When grafts from GTKO/CD46 pigs were transplanted with blockade of both pathways, a minimal or insignificant adaptive response was documented. When a GTKO/CD46/CIITA-DN graft was transplanted, but no immunosuppressive therapy was administered, a marked adaptive response was documented. In the presence of CD28/B7 pathway blockade (abatacept or belatacept), there was a weak adaptive response that was diminished when compared with that to a GTKO/CD46 graft. Blockade of both pathways prevented an adaptive response. Although expression of the mutant MHC CIITA-DN gene was associated with a reduced adaptive immune response when immunosuppressive therapy was inadequate, when blockade of both the CD40/CD154 and CD28/B7 pathways was present, the response even to a GTKO/CD46 graft was suppressed. This was confirmed after GTKO/CD46 heart transplantation in baboons.
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影响因子:
3.1
作者:
Hara, Hidetaka;Long, Cassandra;Cooper, David K. C.
通讯作者:
Cooper, David K. C.
影响因子:
6.2
作者:
Haanstra, KG;Sick, EA;Jonker, M
通讯作者:
Jonker, M
影响因子:
82.9
作者:
Cardona, K;Korbutt, GS;Larsen, CP
通讯作者:
Larsen, CP
DOI:
10.1111/j.1600-6143.2011.03736.x
发表时间:
2012-01
期刊:
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子:
--
作者:
Badell IR;Thompson PW;Turner AP;Russell MC;Avila JG;Cano JA;Robertson JM;Leopardi FV;Strobert EA;Iwakoshi NN;Reimann KA;Ford ML;Kirk AD;Larsen CP
通讯作者:
Larsen CP
影响因子:
3.9
作者:
Ezzelarab, Mohamed B.;Ekser, Burcin;Cooper, David K. C.
通讯作者:
Cooper, David K. C.