MECHANISMS OF TOLERANCE AND AUTOIMMUNITY IN THE EYE

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DESCRIPTION (Adapted from the Applicant's abstract): The eye is considered to be an immunologically privileged site in which potentially sight threatening immune responses must be inhibited. This application proposes studies to investigate this issue by studying the basic mechanisms by which T-cells recognize and respond to antigens that are present in the eye. In the first aim, a novel adoptive transfer system employing ovalbumin (OVA) specific T-cells from the DO11.10 TCR transgenic mouse will be used to study lymphatic and splenic drainage from the eye and to determine the role of intraocular antigen presenting cells (APC) in presenting antigens from the eye. In the second aim, transgenic mice will be produced that express OVA in the retina as a model self antigen. The ability of OVA specific T-cells activated in various ways to infiltrate the eye in response to exogenous or endogenous OVA will be studied. The role of Fas ligand expression within the eye on the induction of apoptosis of the infiltrating cells will be determined. In the third aim, transgenic mice expressing either secreted or membrane OVA in the retina will be crossed with the DO11.10 TCR transgenic mouse or given DO11.10 T-cells by adoptive transfer and the degree and cellular mechanisms of tolerance induction will be assessed.