PMID- 11024130 OWN - NLM STAT- MEDLINE DCOM- 20001120 LR - 20190508 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 74 IP - 21 DP - 2000 Nov TI - Incoming human cytomegalovirus pp65 (UL83) contained in apoptotic infected fibroblasts is cross-presented to CD8(+) T cells by dendritic cells. PG - 10018-24 AB - 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. FAU - Arrode, G AU - Arrode G AD - INSERM U395, IFR 30, UPS, CNRS, CHU, 31024 Toulouse Cedex, France. FAU - Boccaccio, C AU - Boccaccio C FAU - Lule, J AU - Lule J FAU - Allart, S AU - Allart S FAU - Moinard, N AU - Moinard N FAU - Abastado, J P AU - Abastado JP FAU - Alam, A AU - Alam A FAU - Davrinche, C AU - Davrinche C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Phosphoproteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Viral Matrix Proteins) RN - 0 (cytomegalovirus matrix protein 65kDa) SB - IM MH - *Antigen Presentation MH - Antigen-Presenting Cells MH - Apoptosis MH - Cell Line MH - Cytomegalovirus/*immunology MH - Dendritic Cells/*immunology MH - Fibroblasts/*virology MH - Humans MH - Lymphocyte Activation MH - Phosphoproteins/*immunology MH - T-Lymphocytes, Cytotoxic/*immunology MH - Tumor Necrosis Factor-alpha/pharmacology MH - Viral Matrix Proteins/*immunology PMC - PMC102040 EDAT- 2000/10/12 11:00 MHDA- 2001/02/28 10:01 PMCR- 2000/11/01 CRDT- 2000/10/12 11:00 PHST- 2000/10/12 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/10/12 11:00 [entrez] PHST- 2000/11/01 00:00 [pmc-release] AID - 0711 [pii] AID - 10.1128/jvi.74.21.10018-10024.2000 [doi] PST - ppublish SO - J Virol. 2000 Nov;74(21):10018-24. doi: 10.1128/jvi.74.21.10018-10024.2000.