September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
The lectin but not classical pathway of activation is important for complement to regulate the development of experimental autoimmune uveitis
Author Affiliations & Notes
  • Lingjun Zhang
    Immunology, Cleveland Clinic, Cleveland, Ohio, United States
  • Brent A Bell
    Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, United States
  • Yan Li
    Immunology, Cleveland Clinic, Cleveland, Ohio, United States
  • Xiaomin Zhang
    Eye Institute, Tianjin Medical University Eye Hospital, Tianjin, China
  • John Fung
    Digestive Diseases Institute, Cleveland Clinic, Cleveland, Ohio, United States
  • Rachel R Caspi
    National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  • Feng Lin
    Immunology, Cleveland Clinic, Cleveland, Ohio, United States
  • Footnotes
    Commercial Relationships   Lingjun Zhang, None; Brent Bell, None; Yan Li, None; Xiaomin Zhang, None; John Fung, None; Rachel Caspi, None; Feng Lin, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      Lingjun Zhang, Brent A Bell, Yan Li, Xiaomin Zhang, John Fung, Rachel R Caspi, Feng Lin; The lectin but not classical pathway of activation is important for complement to regulate the development of experimental autoimmune uveitis. Invest. Ophthalmol. Vis. Sci. 201657(12):.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : Complement needs to be activated to function. Although the alternative pathway has been found important in regulating T cell responses, the potential roles of the other two complement activation pathways, the classical and the lectin pathways in this process remain unclear. To address this issue, we studied mice deficient of C4 (both classical and lectin pathways deficient) or C1q (classical pathway deficient) in the development of experimental autoimmune uveitis (EAU).

Methods : WT, C4 and C1q knockout (KO) mice (all C57BL/6J background) were immunized with interphotoreceptor retinoid binding protein (IRBP) peptide to induce EAU following an established protocol. After immunization, the development of EAU was monitored by indirect ophthalmoscopy, and clinical scores were assigned according to previously published criteria. Two weeks after immunization, mice were also examined by scanning laser ophthalmoscopy (SLO) and spectral-domain optical coherence tomography (OCT). Three weeks after immunization, mice were euthanized for retinal histopathological analysis, for numbers of antigen-specific CD4+ T cells comparison by tetramer staining, and for antigen-specific Th1/Th17 responses assessment by recall assays.

Results : After immunization, C4 KO mice developed significantly milder EAU than WT controls while C1q KO mice developed comparable EAU to WT mice as judged by clinical scores, retinal histopathological scores, SLO and OCT analyses. Consistent with the imaging results, C4 KO mice in EAU also showed reduced numbers of IRBP-specific CD4+ T cells and had decreased IRBP-specific Th1 and Th17 responses compared with WT mice while C1q mice in EAU did not show any significant difference from WT mice in these immunological assays.

Conclusions : Complement classical pathway of activation is not important for the development of EAU, while the lectin pathway of complement activation is required for the pathological T cell response development in EAU. These data suggest that the lectin pathway of complement activation should be a novel target to suppress pathogenic T cell responses for treating EAU, and potentially, for treating autoimmune uveitis.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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