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Tolerance is dependent on complement C3 fragment iC3b binding to antigen-presenting cells

Nature Medicine volume 9, pages 206–212 (2003)Cite this article

Abstract

Systemic tolerance can be induced by the introduction of antigen into an immune-privileged site. Here we investigated the role of complement in the induction of tolerance after intraocular injection. We found that the development of antigen-specific tolerance is dependent on a complement activation product. The ligation of the complement C3 activation product iC3b to complement receptor type 3 (the iC3b receptor) on antigen-presenting cells resulted in the sequential production of transforming growth factor-β2 and interleukin-10, which is essential for the induction of tolerance. These observations may extend to the development of both neonatal tolerance and other forms of acquired tolerance.

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Figure 1: Role of complement in the in vivo suppression of DTH.
Figure 2: Role of iC3b in suppression of DTH.
Figure 3: Effect of OX-42 (monoclonal antibody against CR3) on suppression of DTH.
Figure 4: Effect of iC3b-CR3 ligation on IL-10 and IL-12.
Figure 5: Analysis of IL-10 and TGF-β2 mRNA expression in OVA-PEC following incubation with iC3b.

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Acknowledgements

We thank J.P. Atkinson for critical review of the data and Y. Wang for help with RT–PCR analysis. This work was supported in part by EY09730, EY10543 and EY 13335, Commonwealth of Kentucky Research Challenge Trust Fund and Research to Prevent Blindness Inc., NY.

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Authors and Affiliations

  1. Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, Kentucky, USA

    Jeong-Hyeon Sohn, Puran S. Bora, Hye-Jung Suk, Henry J. Kaplan & Nalini S. Bora

  2. Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA

    Hector Molina

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Correspondence to Nalini S. Bora.

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Sohn, JH., Bora, P., Suk, HJ. et al. Tolerance is dependent on complement C3 fragment iC3b binding to antigen-presenting cells. Nat Med 9, 206–212 (2003). https://doi.org/10.1038/nm814

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