The immunological privilege of the anterior chamber is due in large part to the down regulation of delayed-type hypersensitivity that is uniquely induced when antigens are introduced into this ocular compartment and which has been termed anterior chamber-associated immune deviation (ACAID). Corneal allografts enjoy a privileged status and experience the lowest rejection rate of all forms of solid tissue grafts. The present research project will examine the interaction between these two ocular components and consider the hypothesis that the cornea and the anterior chamber conspire to promote the acceptance of corneal allografts and the maintenance of the immune privilege of the anterior chamber. A series of in vivo studies will determine if corneal allografts are capable of inducing down-regulation of allograft immunity (i.e., ACAID) and thereby inhibit corneal graft rejection. Other investigations will determine if induction of ACAID prior to corneal grafting produces graft enhancement and reduces the incidence of rejection of highly immunogenic, """"""""high risk"""""""" corneal allografts. The second major specific aim will define the immunogenetic boundaries of ACAID and determine which specific categories of histocompatibility antigens can induce ACAID and which do not. The third specific aim will test the hypothesis that splenic B cells play a crucial role in the induction of ACAID and are the integral component responsible for the well-recognized splenic requirement for the induction of ACAID. The fourth specific aim seeks to alter the pattern of immunological rejection of syngeneic intraocular tumors. Immune rejection of intraocular tumors can follow one of two T cell-dependent pathways. One pathway inflicts extensive injury to innocent bystander cells by ischemic necrosis. The other pathway rids the eye of the tumor by piecemeal necrosis and produces virtually no injury to juxtaposed normal ocular tissues. Studies involving 4 distinct intraocular regressor tumor models will seek to alter the immunopathological sequelae of intraocular tumor rejection by: (a) the in vivo manipulation of CD4+ and CD8+ T cell subsets; (b) by interfering with cell adhesion molecule interactions; and (c) by altering the intraocular milieu. The long range goals of this project are to understand immune regulatory processes in the eye and to manipulate such processes to reduce immune-mediated injury and corneal graft rejection.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY005631-11
Application #
2159503
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1984-12-01
Project End
1997-11-30
Budget Start
1994-12-01
Budget End
1995-11-30
Support Year
11
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
Ligocki, Ann J; Niederkorn, Jerry Y (2016) Natural Killer T Cells Contribute to Neutrophil Recruitment and Ocular Tissue Damage in a Model of Intraocular Tumor Rejection. Invest Ophthalmol Vis Sci 57:813-23
Ligocki, Ann J; Brown, Joseph R; Niederkorn, Jerry Y (2016) Role of interferon-? and cytotoxic T lymphocytes in intraocular tumor rejection. J Leukoc Biol 99:735-47
Ligocki, Ann J; Niederkorn, Jerry Y (2015) Advances on Non-CD4 + Foxp3+ T Regulatory Cells: CD8+, Type 1, and Double Negative T Regulatory Cells in Organ Transplantation. Transplantation 99:1553-9
Paunicka, Kathryn; Chen, Peter W; Niederkorn, Jerry Y (2012) Role of IFN-? in the establishment of anterior chamber-associated immune deviation (ACAID)-induced CD8+ T regulatory cells. J Leukoc Biol 91:475-83
Coursey, Terry G; Chen, Peter W; Niederkorn, Jerry Y (2012) IFN-?-independent intraocular tumor rejection is mediated by a macrophage-dependent process that leaves the eye intact. J Leukoc Biol 92:939-50
Coursey, Terry G; Chen, Peter W; Niederkorn, Jerry Y (2011) IL-17-dependent, IFN-gamma-independent tumor rejection is mediated by cytotoxic T lymphocytes and occurs at extraocular sites, but is excluded from the eye. J Immunol 187:4219-28
Coursey, Terry G; Chen, Peter W; Niederkorn, Jerry Y (2011) Abrogating TNF-? expression prevents bystander destruction of normal tissues during iNOS-mediated elimination of intraocular tumors. Cancer Res 71:2445-54
Niederkorn, Jerry Y (2011) Cornea: Window to Ocular Immunology. Curr Immunol Rev 7:328-335
Niederkorn, Jerry Y (2009) Immune escape mechanisms of intraocular tumors. Prog Retin Eye Res 28:329-47
Niederkorn, Jerry Y (2009) Role of NKT cells in anterior chamber-associated immune deviation. Expert Rev Clin Immunol 5:137-144

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