Injection antigen into the anterior chamber (AC) of the eye results in a unique pattern of immune responses known as Anterior Chamber Associated Immune Deviation (ACAID), in which antigen-specific suppressor T-cells (Ts-cells) inhibit systemic delayed type hypersensitivity (DTH). By using dark-reared and light-reared mice (Balb/c) it was previously demonstrated that visible light has a direct effect on this intraocular immune reaction. If light is prevented from reaching the eye by dark-rearing, by placing light reared animals in the dark post AC injection, or by closing the eyelid of light-reared animals in the dark post AC injection, or by closing the eyelid of light-reared animals post AC injection suppression is abolished. Further, it was shown that visible and not ultraviolet or infrared light is responsible for the observed effects. The effect of light was an ocular event and was not developmentally mandated as is visual development, but inducible in adult dark-reared animals. These results showed that there is active intraocular T-cell regulation which prevents suppression in the absence of light. The purpose of this proposal is to further define the cellular and molecular events in the effect of visible light on intraocular immune reactions. The applicant would determine the wavelength responsible for inducing suppressed DTH in order to get an action spectrum that might reflect the nature of the molecular mediators in the effect. He would determine if altering the light/dark conditions changes the distribution and expression in the eye of class I, class II, and other molecules relevant to the immune response (CD4, Thy-1, LCA). He would analyze the regulatory cells induced following AC injection and removal of light from the eyes since these cells are capable of blocking the activity of Ts-cells. Further studies would determine the role of oxygen reactive compounds, neurotransmitters, and neuropeptides play in the light/dark regulation of intraocular immune reactions. The investigator believes that these studies have important implications for understanding intraocular immune responses and possibly the treatment of eye disease.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY008972-01
Application #
3266327
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1991-02-01
Project End
1995-01-31
Budget Start
1991-02-01
Budget End
1992-01-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Griffith, Thomas S; Kazama, Hirotaka; VanOosten, Rebecca L et al. (2007) Apoptotic cells induce tolerance by generating helpless CD8+ T cells that produce TRAIL. J Immunol 178:2679-87
Ferguson, Thomas A; Griffith, Thomas S (2007) The role of Fas ligand and TNF-related apoptosis-inducing ligand (TRAIL) in the ocular immune response. Chem Immunol Allergy 92:140-54
Apte, Rajendra S; Richter, Jennifer; Herndon, John et al. (2006) Macrophages inhibit neovascularization in a murine model of age-related macular degeneration. PLoS Med 3:e310
Unsinger, Jacqueline; Herndon, John M; Davis, Christopher G et al. (2006) The role of TCR engagement and activation-induced cell death in sepsis-induced T cell apoptosis. J Immunol 177:7968-73
Herndon, John M; Stuart, Patrick M; Ferguson, Thomas A (2005) Peripheral deletion of antigen-specific T cells leads to long-term tolerance mediated by CD8+ cytotoxic cells. J Immunol 174:4098-104
Ferguson, Thomas A; Stuart, Patrick M; Herndon, John M et al. (2003) Apoptosis, tolerance, and regulatory T cells--old wine, new wineskins. Immunol Rev 193:111-23
Ferguson, Thomas A; Herndon, John; Elzey, Bennett et al. (2002) Uptake of apoptotic antigen-coupled cells by lymphoid dendritic cells and cross-priming of CD8(+) T cells produce active immune unresponsiveness. J Immunol 168:5589-95
Lee, Hae-Ock; Herndon, John M; Barreiro, Ramon et al. (2002) TRAIL: a mechanism of tumor surveillance in an immune privileged site. J Immunol 169:4739-44
Elzey, B D; Griffith, T S; Herndon, J M et al. (2001) Regulation of Fas ligand-induced apoptosis by TNF. J Immunol 167:3049-56
Kaplan, H J; Leibole, M A; Tezel, T et al. (1999) Fas ligand (CD95 ligand) controls angiogenesis beneath the retina. Nat Med 5:292-7

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