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Efficient presentation of exogenous antigen by liver endothelial cells to CD8+ T cells results in antigen-specific T-cell tolerance

Nature Medicine volume 6, pages 1348–1354 (2000)Cite this article

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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Figure 1: Cross-presentation in LSEC is efficient and depends on the proteasome and TAP.
Figure 2: LSEC induce proliferation of naive CD8+ T cells.
Figure 3: LSEC cross-present antigen after antigen uptake in vivo.
Figure 4: LSEC cross-present ovalbumin to CD8+ T cells in vivo.
Figure 5: Antigen-presentation by LSEC leads to tolerance induction in CD8+ T cells.

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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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Author notes

  1. Andreas Limmer and Jutta Ohl: A.L. and J.O. contributed equally to this work.

Authors and Affiliations

  1. Zentrum für Molekulare Biologie Heidelberg (ZMBH), Heidelberg, 69120, Germany

    Andreas Limmer, Jutta Ohl & Percy A. Knolle

  2. Department of Nephrology, Medizinische Hochschule Hannover, Hannover, Germany

    Christian Kurts

  3. Microbiology and Tumor Biology Center, Karolinska-Institutet, Stockholm, Sweden

    Hans-Gustaf Ljunggren

  4. Department of Biochemistry, Tel Aviv University, Israel

    Yuval Reiss

  5. Research Department, Cantonal Hospital St. Gall, Switzerland

    Marcus Groettrup

  6. Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, 69120, Germany

    Frank Momburg & Bernd Arnold

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Correspondence to Percy A. Knolle.

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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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