The role of Fas ligand and TNF-related apoptosis-inducing ligand (TRAIL) in the ocular immune response.

The host response to pathogenic insults involves complex inflammatory responses and cellular immune reactions. While these are central to host defense and vital to clearing dangerous invaders, they are often associated with nonspecific injury to nearby tissue. These localized reactions function to successfully deal with pathogens before they spread to other areas. They are generally effective since most organ systems can tolerate these responses without permanent consequences. There are sites, however, that prohibit the spread of inflammation because these episodes can threaten organ integrity and function. The most prominent examples of these are the eye, brain, and reproductive organs (testis and ovary) where even minor bouts of inflammation can have long-term consequences on the survival of the organism. In these areas, immune responses either do not proceed, or proceed in a manner different from other areas; thus, they are called 'immunologically privileged'. Studies by a number of laboratories have determined that there are a number of mediators of ocular immune privilege. These include locally produced immunosuppressive cytokines, neuropeptides, limited expression of major histocompatibility complex class I and class II, complementregulatory proteins, immune deviation, natural killer cell inhibitors, and the expression of the death-inducing ligands Fas ligand (FasL) and tumor necrosis factor (TNF)-related apoptosisinducing ligand (TRAIL). The death-inducing molecules are poised to effectively deal with inflammatory cells once they pass the natural barriers of the eye, and effectively limit the spread of inflammatory cells and tumor cells within the confines of the eye by inducing apoptosis. The function of FasL and TRAIL will be the subject of this chapter.