Abstract
Myeloid antigen-presenting cells (APC) are known to cross-present exogenous antigen on major histocompatibility class I molecules to CD8+ T cells and thereby induce protective immunity against infecting microorganisms. Here we report that liver sinusoidal endothelial cells (LSEC) are organ-resident, non-myeloid APC capable of cross-presenting soluble exogenous antigen to CD8+ T cells. Though LSEC employ similar molecular mechanisms for cross-presentation as dendritic cells, the outcome of cross-presentation by LSEC is CD8+ T cell tolerance rather than immunity. As uptake of circulating antigens into LSEC occurs efficiently in vivo, it is likely that cross-presentation by LSEC contributes to CD8+ T cell tolerance observed in situations where soluble antigen is present in the circulation.
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Acknowledgements
The authors thank S. Hegenbarth and A. Klevenz for technical assistance; N. Shastri for providing the ovalbumin-specific T-cell hybridoma B3Z, H. Rammensee for providing β-gal–specific T-cell clone 0805B; and L. Eisenbach and A. Porgador for supplying us with Kb-SIINFEKL-specific antibody 25-D1.16. This work was supported by a grant from the Deutsche Forschungsgemeinschaft to P.A.K. (Kn 437/1-5 and SFB 405 project A7) and a European Union grant to B.A. (BIO-97-2151).
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Limmer, A., Ohl, J., Kurts, C. et al. Efficient presentation of exogenous antigen by liver endothelial cells to CD8+ T cells results in antigen-specific T-cell tolerance. Nat Med 6, 1348–1354 (2000). https://doi.org/10.1038/82161
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DOI: https://doi.org/10.1038/82161
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