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Journal of Virology, November 2000, p. 10018-10024, Vol. 74, No. 21
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Incoming Human Cytomegalovirus pp65 (UL83) Contained in Apoptotic Infected Fibroblasts Is Cross-Presented to CD8+ T Cells by Dendritic Cells

Géraldine Arrode,1 Claire Boccaccio,2 Jacqueline Lulé,1 Sophie Allart,1 Nathalie Moinard,1 Jean-Pierre Abastado,2 Antoine Alam,1 and Christian Davrinche1,*

INSERM U395, IFR 30, UPS, CNRS, CHU, 31024 Toulouse Cédex,1 and LUTI-IDM, Institut de Recherches Biomédicales des Cordeliers, 75006 Paris,2 France

Received 20 April 2000/Accepted 20 July 2000

Human cytomegalovirus (HCMV) infection is well controlled mainly by cytotoxic CD8+ T lymphocytes (CTL) directed against the matrix protein pp65 despite the numerous immune escape mechanisms developed by the virus. Dendritic cells (DCs) are key antigen-presenting cells for the generation of an immune response which have the capacity to acquire antigens via endocytosis of apoptotic cells and thus present peptides to major histocompatibility complex class I-restricted T cells. We examined whether this mechanism could contribute to the activation of anti-pp65 CTL. In this study, we show that infection by HCMV AD169 induced sensitization of MRC5 fibroblasts to tumor necrosis factor alpha-mediated apoptosis very early after virus inoculation and that pp65 contained in apoptotic cells came from the delivery of the matrix protein into the cell. We observed that immature DCs derived from peripheral monocytes were not permissive to HCMV AD169 infection but were able to internalize pp65-positive apoptotic infected MRC5 cells. We then demonstrated that following exposure to these apoptotic bodies, DCs could activate HLA-A2- or HLA-B35-restricted anti-pp65 CTL, suggesting that they acquired and processed properly fibroblast-derived pp65. Together, our data suggest that cross-presentation of incoming pp65 contained in apoptotic cells may provide a quick and efficient way to prime anti-HCMV CD8+ T cells.

* Corresponding author. Mailing address: INSERM U395, IFR 30, UPS, CNRS, CHU, BP 3028, 31024 Toulouse Cédex, France. Phone: 33 5 62 74 83 85. Fax: (33) 5 62.74.83.86. E-mail: davrinch{at}purpan.inserm.fr.

Journal of Virology, November 2000, p. 10018-10024, Vol. 74, No. 21
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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