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Originally published In Press as doi:10.1167/iovs.08-3264 on May 14, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:3778-3782.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-3264
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Role of DAF in Protecting against T-Cell Autoreactivity that Leads to Experimental Autoimmune Uveitis

Fengqi An,1,2 Qing Li,1,2,3 Zhidan Tu,1,3 Hong Bu,3 Chi-Chao Chan,4 Rachel R. Caspi,4 and Feng Lin1

1From the Institute of Pathology, Case Western Reserve University, Cleveland, Ohio; the 3Department of Pathology, Sichuan University, Chengdu, China; and the 4Department of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland.

PURPOSE. To investigate the role of decay-accelerating factor (DAF), a cell surface complement regulator that recently has been linked to T-cell responses and autoimmunity in the pathogenesis of experimental autoimmune uveitis (EAU).

METHODS. EAU was induced in wild-type (WT) and Daf1–/– mice, and their disease severities, IRBP specific Th1/Th17 responses, and cytokine expression profiles were compared. In a test of the efficacy of treatment with soluble mouse DAF protein, EAU was induced in disease-susceptible B10.RIII mice, and they were treated with 0.5 mg soluble DAF protein or equal volume of PBS IP every other day. Retinal histology and IRBP-specific T-cell responses were compared after 14 days.

RESULTS. Both EAU incidence and histopathology scores were significantly greater in Daf1–/– mice. There was a >10-fold greater mononuclear cell influx into the retina together with severe vasculitic lesions, retinal folding, and photoreceptor cell layer destruction. There were 5- to 7-fold greater Th1 and 3- to 4-fold greater Th17 responses against IRBP in Daf1–/– mice with EAU, and they expressed significantly elevated levels of GM-CSF, IL-2, IL-3, and IFN-{gamma}. WT B10.RIII mice that received soluble DAF protein treatments exhibited decreased IRBP-specific Th1/Th17 responses and were protected from retinal injury compared with the mice that received PBS treatments.

CONCLUSIONS. DAF significantly influences IRBP-specific Th1 and Th17 responses and disease severity in EAU. Systemic upregulation of DAF levels could be used to suppress retinal antigen(s)–specific autoimmunity to treat autoimmune posterior uveitis.






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