Nature Medicine
7, 807 - 813 (2001)
doi:10.1038/89930
Apoptotic cells overexpress vinculin and induce vinculin-specific cytotoxic T-cell cross-primingAntonella Propato1, 7, Giovanna Cutrona2, 7, Vittorio Francavilla1, Massimo Ulivi2, 3, Enrico Schiaffella1, Olfert Landt3, Rod Dunbar4, Vincenzo Cerundolo4, Manlio Ferrarini2, 5, 7
& Vincenzo Barnaba1, 61
Fondazione Andrea Cesalpino, Dipartimento di Medicina Interna, Università degli Studi di Roma La Sapienza, Rome, Italy
2
Servizio di Immunologia Clinica, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
3
TIB-Mol Biol, Berlin, Germany
4
Institute of Molecular Medicine, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK
5
Dipartimento di Oncologia Biologia e Genetica, Università degli Studi di Genova, Genoa, Italy
6
Istituto Pasteur-Cenci Bolognetti, Rome, Italy
7
A.P., G.C. and M.F. contributed equally to this study.
Correspondence should be addressed to Vincenzo Barnaba vincenzo.barnaba@uniroma1.itHere 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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