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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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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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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DOI: https://doi.org/10.1038/nm814