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CUTTING EDGE |
*
Divisione di Medicina II, Laboratorio di Immunologia dei Tumori, and
Unità di Immunochimica, Department of Biological and Technical Research, Istituto Scientifico H S. Raffaele and University of Milan, Milan, Italy; and
Consiglio Nazionale delle Ricerche Molecular and Cellular Pharmacology Center, Milan, Italy
Physiologic cell death via apoptosis occurs without
inflammation or autoimmunity. Here, we investigated the outcome of the
interaction of apoptotic cells with dendritic cells (DCs), which are
potent professional APCs. DCs internalized apoptotic cells and
processed them for presentation to both MHC class I- and class
II-restricted T cells with an efficiency that was dependent upon the
number of apoptotic cells. The latter event was accompanied by the
autocrine/paracrine secretion of IL-1ß and TNF-
, with eventual DC
maturation. High numbers of apoptotic cells, mimicking a failure of
their in vivo clearance, are therefore sufficient to trigger DC
maturation and the presentation of intracellular Ags from apoptotic
cells, even in the absence of exogenous "danger"
signals.
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A. Ronchetti, P. Rovere, G. Iezzi, G. Galati, S. Heltai, M. P. Protti, M. P. Garancini, A. A. Manfredi, C. Rugarli, and M. Bellone Immunogenicity of Apoptotic Cells In Vivo: Role of Antigen Load, Antigen-Presenting Cells, and Cytokines J. Immunol., July 1, 1999; 163(1): 130 - 136. [Abstract] [Full Text] [PDF]
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M. L. Jelachich, C. Bramlage, and H. L. Lipton Differentiation of M1 Myeloid Precursor Cells into Macrophages Results in Binding and Infection by Theiler's Murine Encephalomyelitis Virus and Apoptosis J. Virol., April 1, 1999; 73(4): 3227 - 3235. [Abstract] [Full Text]
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P. Chaux, V. Vantomme, V. Stroobant, K. Thielemans, J. Corthals, R. Luiten, A. M.M. Eggermont, T. Boon, and P. van der Bruggen Identification of MAGE-3 Epitopes Presented by HLA-DR Molecules to CD4+ T Lymphocytes J. Exp. Med., March 1, 1999; 189(5): 767 - 778. [Abstract] [Full Text] [PDF]
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V. Russo, S. Tanzarella, P. Dalerba, D. Rigatti, P. Rovere, A. Villa, C. Bordignon, and C. Traversari Dendritic cells acquire the MAGE-3 human tumor antigen from apoptotic cells and induce a class I-restricted T cell response PNAS, February 29, 2000; 97(5): 2185 - 2190. [Abstract] [Full Text] [PDF]
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