Delayed allograft rejection by the suppression of class II transactivator.
- Author:
Tae Woon KIM
1
;
Young Mi CHOI
;
Jae Nam SEO
;
Ju Hyun KIM
;
Young Ho SUH
;
Doo Hyun CHUNG
;
Kyeong Cheon JUNG
;
Kwon Ik OH
Author Information
1. Department of Pathology, Hallym University College of Medicine, Chuncheon 200-702, Korea. kwonik@hallym.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
graft rejection;
melanoma, experimental;
MHC class II transactivator protein;
neoplasm transplantation;
transplantation, homologous
- MeSH:
Transplantation, Homologous;
Transfection;
Trans-Activators/genetics/*immunology/metabolism;
Trans-Activation (Genetics)/genetics/immunology;
Skin Transplantation;
Nuclear Proteins/genetics/*immunology/metabolism;
Mutation;
Mice, Transgenic;
Mice, Knockout;
Mice, Inbred C57BL;
Mice, Inbred BALB C;
Mice;
Melanoma, Experimental/genetics/immunology/pathology;
Male;
Interferon Type II/pharmacology;
Humans;
Histocompatibility Antigens Class II/genetics/*immunology/metabolism;
Graft Survival/genetics/immunology;
Graft Rejection/genetics/*immunology;
Genes, MHC Class II/genetics/immunology;
Flow Cytometry;
DNA, Complementary/genetics;
Cell Proliferation/drug effects;
Cell Line, Tumor;
Animals
- From:Experimental & Molecular Medicine
2006;38(3):210-216
- CountryRepublic of Korea
- Language:English
-
Abstract:
We examined the effect of class II transactivator (CIITA) down-modulation on allograft rejection. To inhibit the function of CIITA, we constructed a series of CIITA mutants and found one exhibiting the dominant-negative effect on the regulation of major histocompatibility complex (MHC) class II expression. To test whether the CIITA dominant-negative mutant reduces immunogenecity, CIITA-transfected melanoma cells were injected into allogeneic host and assessed for immune evading activity against host immune cells. We demonstrated that the CIITA dominant-negative mutant allowed tumor nodules to develop earlier in the lung than control by this tumor challenge study. Furthermore, skin grafts deficient for CIITA also survived longer than wild-type in allogeneic hosts. Both the tumor challenge and skin graft studies suggest the inhibition of CIITA molecules in donor tissue would be beneficial to the control of allo-response.
