The role of the class II transactivator (CIITA) in MHC class I and II regulation and graft rejection in kidney.
Class II transactivator (CIITA) induces transcription of MHC class II genes, and induces class I in some cell lines. We examined the effect of CIITA deficiency on class I and II expression in mouse kidney. In CIITA knockout (CIITAKO) mice, basal class II was absent, but class I levels were mildly but significantly increased. Allogeneic stimulation or ischemic injury increased class I and II expression in kidneys of control (wild-type, WT) mice but induced only class I in CIITAKO mice. Thus, in kidney, all basal and induced class II expression was CIITA-dependent, but neither basal nor induced class I was CIITA-dependent. Rejecting kidney allografts from CIITAKO mice in CBA hosts manifested intense induction of donor class I but no donor class II expression. Rejecting kidneys from both WT and CIITAKO donors showed predominantly CD8 T-cell infiltration at days 7 and 21, with increasing tubulitis and arteritis at day 21. CIITAKO kidneys showed fewer infiltrating cells than WT kidneys at day 21. Thus CIITA-deficient kidneys have no basal and induced class II expression but display intense induction of class I expression, and evoke typical rejection lesions, although some indices of infiltration are reduced at day 21.
Sims
T N
TN
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.
Afrouzian
M
M
Urmson
J
J
Zhu
L F
LF
Halloran
P F
PF
D000818:Animals; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006720:Homozygote; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D008285:Major Histocompatibility Complex; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis; D009687:Nuclear Proteins; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators