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The Role of the Class II Transactivator (CIITA) in MHC Class I and II Regulation and Graft Rejection in Kidney
Author(s) -
Sims Tasha N.,
Afrouzian Marjan,
Urmson Joan,
Zhu LinFu,
Halloran Philip F.
Publication year - 2001
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1034/j.1600-6143.2001.001003211.x
Subject(s) - ciita , medicine , mhc class ii , cd74 , class (philosophy) , transactivation , kidney transplant , major histocompatibility complex , kidney transplantation , immunology , kidney , immune system , genetics , transcription factor , biology , gene , artificial intelligence , computer science
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.