The anterior chamber of the eye is endowed with remarkable properties which either prevent or significantly delay the acute rejection of various allografts. Immune privilege of the anterior chamber is a composite of several independent mechanisms which conspire to prevent the induction and execution of certain forms of inflammation. One of these mechanisms is the down-regulation of delayed-type hypersensitivity (DTH) that occurs when antigens are introduced into the anterior chamber and which has been termed anterior chamber-associated immune deviation (ACAID). ACAID appears to be an immunological compromise which protects the eye from immune-mediated injury while preserving other immune effector mechanisms that protect against life-threatening pathogens. This project will analyze the underlying mechanisms which lead to the induction of ACAID. The first specific aim will test the hypothesis that ACAID is the consequence of the preferential activation of a Th2 population which cross-regulates Th1 cells thereby inhibiting DTH. Although most antigenes induce ACAID, many do not and instead, provoke robust systemic DTH. The second specific aim will identify those characteristics which determine whether or not an antigen will induce ACAID. The third specific aim will test the hypothesis that splenic B cells reprocess antigens that are carried from the eye to the spleen. The hypothesis predicts that antigens are released by emigrating antigen presenting cells and are captured by splenic B cells which present peptide fragments to T cells leading to the generation of T suppressor cells. The long range goal of this project is to gain a clear understanding of the various immunoregulatory processes unique to the eye and which protect the delicate ocular tissues from unwitting immune-mediated injury that can lead to blindness. This information will be useful in devising strategies to either enhance immune privilege in conditions which benefit the host (e.g., corneal transplantation) or abrogate immune privilege to protect against sight- and life-threatening neoplasms.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Study Section
Visual Sciences A Study Section (VISA)
Program Officer
Finerty, John F
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University of Texas Sw Medical Center Dallas
Schools of Medicine
United States
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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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