DAF Protects Against T Cell Autoreactivity That Leads To Experimental Autoimmune Uveitis
Fengqi An 1,
Qing Li 1,
zhidan Tu 1,
Hong Bu 2,
Chi-Chao Chan 3,
Rachel R Caspi 3,
and
Feng Lin 4*
1 Pathology, Case Western Reserve University, Cleveland, Ohio, United States
2 Pathology, Sichuan University, Chengdu, China
3 National Eye Institute, Bethesda, Maryland, United States
4 Pathology, Case Western Reserve University, 2085 Adelbert Rd, Cleveland, Ohio, 44106, United States
* To whom correspondence should be addressed. E-mail: feng.lin{at}case.edu.
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Abstract |
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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: We induced EAU in WT and Daf1-/- mice and compared their disease severities, IRBP specific Th1/Th17 responses and cytokine expression profiles. To test the efficacy of treatment with soluble mouse DAF protein, we induced EAU in disease susceptible B10.RIII mice and treated them with 0.5 mg soluble DAF protein or equal volume of PBS i.p. every other day. We compared retinal histology and IRBP specific T cell responses in 14 days as done above.
Results: We found that both EAU incidence and histopathology scores were significantly greater in Daf1-/- mice. There were >10 fold greater mononuclear cell influx into the retina together with severe vasculitic lesions, retinal folding and photoreceptor cell layer destruction. There were 5-7 fold greater Th1 and 3-4 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-
. WT B10.RIII mice that received soluble DAF protein treatments exhibited decreased IRBP specific Th1/Th17 responses and were protected from retinal injury compared to mice 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.
Key Words:
autoimmune response/disease, immunoregulation, immunotherapy, uveitis
