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Apoptotic cells overexpress vinculin and induce vinculin-specific cytotoxic T-cell cross-priming

Nature Medicine volume 7, pages 807–813 (2001)Cite this article

Abstract

Here we show that apoptotic cells overexpress vinculin and are ingested by dendritic cells, which subsequently cross-prime vinculin-specific cytotoxic T lymphocytes (CTLs). Successful cross-priming requires that the apoptotic cells provide maturation signals to dendritic cells through CD40–CD40 ligand (CD40L) interactions. If apoptotic cells are CD40L−, the help of a third T cell is needed for priming, indicating a regulatory role for apoptotic cells in determining priming or tolerance. Vinculin-specific CTL priming is also related to apoptosis in vivo, given that in HIV-seropositive individuals, the frequency of specific CTLs depends on the proportion of peripheral CD40L+ apoptotic cells.

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Figure 1: Vinculin expression by apoptotic H9 T cells.
Figure 2: Immature dendritic cells phagocytose apoptotic cells and mature following exposure to CD40L+ apoptotic cells.
Figure 3: Cross-priming of vinculin-specific CD8+ T cell responses in vitro by dendritic cells (DC) that have captured and processed vinculin expressing CD40L+ apoptotic cells (AC).
Figure 4: Correlation between the frequency of vinculin-specific CTLs, viral load and number of peripheral apoptotic cells in HIV-infected patients, during anti-retroviral therapy.
Figure 5: The magnitude of vinculin-specific CTL responses is related directly to the levels of circulating CD40L+ apoptotic cells and inversely to the CD4+ T-cell numbers in HIV-infected patients.

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Acknowledgements

We thank F. Di Rosa for discussions and critical reading of the manuscript and C. Mastroianni for providing us the HIV-infected patients. This work was supported by Ministero della Sanità-Istituto Superiore di Sanità (Progetti AIDS 1998 to V.B. and M.F., and Epatite Virale 1997 to V.B.).; Ministero dell'Università e della Ricerca Scientifica e Tecnologica 40% 1997–1998 to V.B.; Progetto Associazione Italiana Sclerosi Multipla (AISM) 1997–1998 to V.B.; Progetto Finalizzato CNR 'Biotecnologie' to V.B.; European Community Contract No. BMH4-CT98-3703 to V.B.; and Associazione Italiana per la Ricerca sul Cancro (AIRC) 1999 to M.F.

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Author notes

  1. Antonella Propato, Giovanna Cutrona and Manlio Ferrarini: A.P., G.C. and M.F. contributed equally to this study.

Authors and Affiliations

  1. Dipartimento di Medicina Interna, Fondazione Andrea Cesalpino, Università degli Studi di Roma La Sapienza, Rome, Italy

    Antonella Propato, Vittorio Francavilla, Enrico Schiaffella & Vincenzo Barnaba

  2. Servizio di Immunologia Clinica, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

    Giovanna Cutrona, Massimo Ulivi & Manlio Ferrarini

  3. TIB-Mol Biol, Berlin, Germany

    Massimo Ulivi & Olfert Landt

  4. Nuffield Department of Medicine, Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK

    Rod Dunbar & Vincenzo Cerundolo

  5. Dipartimento di Oncologia Biologia e Genetica, Università degli Studi di Genova, Genoa, Italy

    Manlio Ferrarini

  6. Istituto Pasteur-Cenci Bolognetti, Rome, Italy

    Vincenzo Barnaba

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Correspondence to Vincenzo Barnaba.

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Propato, A., Cutrona, G., Francavilla, V. et al. Apoptotic cells overexpress vinculin and induce vinculin-specific cytotoxic T-cell cross-priming. Nat Med 7, 807–813 (2001). https://doi.org/10.1038/89930

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