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A CIITA-independent pathway of MHC class II expression has been found in the eye and the brain, both immune-privileged sites. Although corneal endothelial cells were unable to express MHC class II in response to IFN-gamma alone, these cells readily expressed MHC class II molecules via a CIITA-independent pathway when triggered by simultaneous exposure to IFN-gamma and TNF-alpha. CIITA-independent expression of MHCclass II molecules enabled corneal endothelial cells to present cytosolic, but not endosomal, ovalbumin (OVA) to OVA-primed T cells. To determine whether CIITA-independent expression of MHC class II is relevant in vivo, minor H-only-incompatible corneal allografts prepared from CIITA knockout (KO) mice, MHC class II KO mice or wild-type donors were placed in eyes of normal mice. Cornea allografts from wild-type and CIITA KO mice suffered similar rejection fates, whereas far fewer class II-deficient corneas were rejected. In addition, MHC class II-bearing macrophages were observed in cuprizone-induced inflammatory and demyelinating brain lesions of CIITA KO mice. We conclude that class II expression via the CIITA-independent pathway enhances the vulnerability to rejection of corneal grafts expressing minor antigens. The potential relevance of CIITA-independent MHC class II expression at immune-privileged sites is discussed in relation to tolerance to strong autoantigens.

Type

Journal article

Journal

European journal of immunology

Publication Date

02/2004

Volume

34

Pages

471 - 480

Addresses

Schepens Eye Research Institute, Harvard Medical School, Boston, USA. arancibia@rics.bwh.harvard.edu

Keywords

Brain, Cornea, Endothelium, Endothelial Cells, Animals, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Mice, Tumor Necrosis Factor-alpha, Trans-Activators, Nuclear Proteins, Antigens, Differentiation, B-Lymphocyte, Interleukin-2, Antigens, Bacterial, Histocompatibility Antigens Class II, Corneal Transplantation, Flow Cytometry, Genes, MHC Class II, Transcription, Genetic, Up-Regulation, Male, Interferon-gamma