Fas Ligand-Induced Apoptosis as a Mechanism of Immune Privilege

TLDR

The eye is a privileged site that cannot tolerate destructive inflammatory responses. Inflammatory cells entering the eye’s anterior chamber during viral infection undergo Fas/FasL‑dependent apoptosis, preventing tissue damage. Loss of FasL in gld mice leads to ocular inflammation without apoptosis, while Fas‑positive tumor cells are eliminated by apoptosis in normal but not FasL‑deficient eyes, demonstrating that Fas‑FasL interactions preserve immune privilege.

Abstract

The eye is a privileged site that cannot tolerate destructive inflammatory responses. Inflammatory cells entering the anterior chamber of the eye in response to viral infection underwent apoptosis that was dependent on Fas (CD95)-Fas ligand (FasL) and produced no tissue damage. In contrast, viral infection in gld mice, which lack functional FasL, resulted in an inflammation and invasion of ocular tissue without apoptosis. Fas-positive but not Fas-negative tumor cells were killed by apoptosis when placed within isolated anterior segments of the eyes of normal but not FasL-negative mice. FasL messenger RNA and protein were detectable in the eye. Thus, Fas-FasL interactions appear to be an important mechanism for the maintenance of immune privilege.