Delayed allograft rejection by the suppression 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 immunogenicity, 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.
Kim
Tae Woon
TW
Department of Pathology, Hallym University College of Medicine, Chuncheon 200-702, Korea.
Choi
Young Mi
YM
Seo
Jae Nam
JN
Kim
Ju Hyun
JH
Suh
Young Ho
YH
Chung
Doo Hyun
DH
Jung
Kyeong Cheon
KC
Oh
Kwon Ik
KI
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D005434:Flow Cytometry; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology*; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008297:Male; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016038:Skin Transplantation; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics / Q000276:immunology; D014162:Transfection; D014184:Transplantation, Homologous
D018076:DNA, Complementary; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D007371:Interferon-gamma