The Role of the Class II Transactivator (CIITA) in MHC Class I and II Regulation and Graft Rejection in Kidney

Abstract

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.