Role of T cells in bacteria-induced Lens-Associated Uveitis (LAU)
Purpose. To determine if T cell depletion diminishes the severity of inflammation in a model for LAU induced by antigens from P. acnes. Classically, LAU is believed to be mediated by complement-fixing antibodies against lens crystalline. In bacteria-induced LAU, prior immunization to the specific bacterial antigen is required, and the lens becomes infiltrated only if a large capsular injury is present. We hypothesize that intraocular T cell activation by bacterial antigens results in the local production of IFN-γ which, in the presence of bacterial toxins, activates intraocular macrophages to nonspecifically mediate lens inflammation. Methods. An antigen/toxin preparation for P. acnes was generated by growing the bacterium in media, followed by killing, lyophilization and resuspension at 10 mg/ml in balanced saline solution. Five groups of eight C57BL6 mice (one naive group and four primed groups) received AC injection of 3 ug of P. acnes antigen in the presence of lens capsule injury. One day prior to AC injection, groups of primed mice received systemic doses of cytotoxic antibodies against CD4, CD8, both or irrelevant control. Seven days later, delayed hypersensitivity (DH) skin responsis were measured and at day 10, the eyes were evaluated by histology for severity of inflammation. Results. In primed mice receiving control antibodies, cutaneous DH was present and ocular histology was characterized by severe lens infiltration with neutrophils surrounded by a zone of granulation tissue (frequency of LAU = 100%, median score = 11.5). As expected, CD4-depleted mice demonstrated diminished cutaneous DH. In addition, the frequency of LAU was significantly reduced (12.5%, p<0.001) and disease severity was significantly less (median score = 3.0, p<0.001). In contrast, CD8 depleted mice demonstrated LAU frequency and severity similar to controls. Conclusions. In bacteria-induced LAU, CD 4 T cells appear to modulate the severity of lens inflammation. Apparently, T cell responsis to non-lens antigens possess the capacity to direct nonspecific "bystander" inflammation against the lens. Supported by NIH grant EY 10327.
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- Ophthalmology & Optometry
- 11 Medical and Health Sciences
- 06 Biological Sciences
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Published In
ISSN
Publication Date
Volume
Issue
Related Subject Headings
- Ophthalmology & Optometry
- 11 Medical and Health Sciences
- 06 Biological Sciences