FAS/FAS ligand-mediated apoptosis as a mechanism of immune privilege

T. A. Ferguson, T. S. Griffith

Research output: Contribution to journalArticlepeer-review

Abstract

The concept of an immune privileged site has been recognized for over 120 years. One such site is the eye, where immune privilege is demonstrated by the remarkable success of comeal grafts and the resistance of this area to the sequelae of damaging inflammatory reactions. We have examined the molecular mechanisms of immune privilege and demonstrate the expression of Fas ligand (FasL) on ocular structures is a major component. Following injection of virus (Herpes simplex virus, type 1; HSV-1) into the eye of C57BL/6 (B6) mice infiltrating inflammatory cells underwent apoptosis and produced no tissue damage. In contrast, viral infection in B6-gld mice (which lack functional FasL), or B6-lpr mice (which lack functional Fas) resulted in an inflammation and invasion of ocular tissue without apoptosis. The expression of functional FasL on ocular tissue was confirmed in vitro when Fastumor cells were killed when placed in isolated anterior segments from normal, but not FasL" mice. Additionally, FasL mRNA was detected in the eye by northern blot and RT-PCR, while FasL protein was detected by immunohistochemistry on the cornea, iris, and retina. Our results show that the induction of apoptosis by Fas-FasL interactions is a potent mechanism of immune privilege and that the consequences of defective FasL for the eye can be the spread of dangerous and unwanted inflammatory responses.

Original languageEnglish (US)
Pages (from-to)A1274
JournalFASEB Journal
Volume10
Issue number6
StatePublished - Dec 1 1996

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