This laboratory has been actively engaged in the study of the eye as an immunologically privileged site using the ACAID model of immunoregulation (ACAID) for Anterior Chamber Associated Immune Deviation). In general, following the introduction of a variety of antigens into the eye, cell mediated responses are actively suppressed, while antibody responses are normal or elevated. It has been shown that this pattern of responses is due to aggressive regulation by various populations of T-cells (10-13) and antigen presenting cells (14). Previous studies from the laboratory have extensively characterized the Ts-cells involved in ACAID, identified a serum borne factor that mediates ACAID, located an antigen presenting cell for TNP-ACAID, identified several cytokines involved in ACAID, and demonstrated that light regulates the suppressed DTH response in ACAID. It is the purpose of these studies to continue this work and further analyze the regulation of the ocular immune response. The investigators will first examine the role of adhesion molecules in the activation of T-cell in the eye. Specifically, T-cell integrins such as VLA-VLA-5, LFA-1, as well as ICAM-1 will be studied by using small synthetic peptides and antibodies that block their function. These types of studies have important implications for drug design. Studies will be done to continue the analysis of the soluble mediators in ACAID. The investigators will also determine the role of T-cell derived cytokine, complement component C5, and soluble T-cell receptor in the ACAID system. In addition, they will look at the regulation of the antibody response following anterior chamber injection of antigen. Understanding the relationship between the immune system and the eye has important implications for the control and treatment of ocular disease.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY006765-13
Application #
2888239
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1988-04-01
Project End
2002-03-31
Budget Start
1999-04-01
Budget End
2000-03-31
Support Year
13
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Washington University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Ferguson, Thomas A; Green, Douglas R (2014) Autophagy and phagocytosis converge for better vision. Autophagy 10:165-7
Zhao, Hui; Roychoudhury, Jayeeta; Doggett, Teresa A et al. (2013) Age-dependent changes in FasL (CD95L) modulate macrophage function in a model of age-related macular degeneration. Invest Ophthalmol Vis Sci 54:5321-31
Mattapallil, Mary J; Wawrousek, Eric F; Chan, Chi-Chao et al. (2012) The Rd8 mutation of the Crb1 gene is present in vendor lines of C57BL/6N mice and embryonic stem cells, and confounds ocular induced mutant phenotypes. Invest Ophthalmol Vis Sci 53:2921-7
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Ferguson, Thomas A; Choi, Jayoung; Green, Douglas R (2011) Armed response: how dying cells influence T-cell functions. Immunol Rev 241:77-88
Griffith, Thomas S; Brincks, Erik L; Gurung, Prajwal et al. (2011) Systemic immunological tolerance to ocular antigens is mediated by TRAIL-expressing CD8+ T cells. J Immunol 186:791-8
Gurung, Prajwal; Kucaba, Tamara A; Schoenberger, Stephen P et al. (2010) TRAIL-expressing CD8+ T cells mediate tolerance following soluble peptide-induced peripheral T cell deletion. J Leukoc Biol 88:1217-25
Unsinger, Jacqueline; Kazama, Hirotaka; McDonough, Jacqueline S et al. (2010) Sepsis-induced apoptosis leads to active suppression of delayed-type hypersensitivity by CD8+ regulatory T cells through a TRAIL-dependent mechanism. J Immunol 184:6766-72
Roychoudhury, Jayeeta; Herndon, John M; Yin, Jiyi et al. (2010) Targeting immune privilege to prevent pathogenic neovascularization. Invest Ophthalmol Vis Sci 51:3560-6

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