Imposing deviant immunity on the presensitized state

Abstract

Delayed hypersensitivity (DH) is an important immune effector modality that successfully wards off intracellular pathogens and many parasites, but also causes immunopathogenic injury to vital tissues. Particularly in the eye, DH has devastating effects that can lead to blindness. Ags injected into the anterior chamber of the eye of naive mice elicit a deviant form of systemic immunity in which DH is selectively down-regulated. Expression of DH in this model system is curtailed by regulatory CD8+ T cells. At present, we have determined whether injection of Ag into the anterior chamber of eyes of specifically sensitized mice also impairs DH expression. Our results indicate that DH is blunted or eliminated in previously primed mice when heterologous proteins, retinal autoantigens, or minor histocompatibility Ags are injected into the anterior chamber. Suppression is achieved in this system by Ag-specific CD8+ T cells, and failed DH can be imposed on immunized mice by i.v. injections of peritoneal exudate cells pulsed with Ag in vitro in the presence of TGF-beta. Thus, the immune regulatory mechanisms that operate to protect the eye from immunogenic inflammation can be invoked in previously sensitized mice. In addition, tolerance could not be generated in presensitized mice by either i.v. injection of soluble Ag or painting of hapten on UVB-exposed skin. It seems that the strategies used by the eye to create a deviant state of immunity in the face of pre-existing conventional immunity may be unique.