Exp Mol Med.  2006 Jun;38(3):210-216.

Delayed allograft rejection by the suppression of class II transactivator

• Kim TW
• Choi YM
• Seo JN
• Kim JH
• Suh YH
• Chung DH
• Jung KC
• Oh KI

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.

Keyword

graft rejection; melanoma, experimental; MHC class II transactivator protein; neoplasm transplantation; transplantation, homologous

MeSH Terms

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