Immature CD4- CD103+ rat dendritic cells induce rapid caspase-independent apoptosis-like cell death in various tumor and nontumor cells and phagocytose their victims.
We previously reported the characterization of a MHC class II(low) CD4- CD103+ (CD4-) subset of dendritic cells (DC) in rat spleen that exhibit a Ca2+-, Fas ligand-, TRAIL- and TNF-alpha-independent cytotoxic activity against specific targets in vitro. In this study, we demonstrate that this DC subset was also found in lymph nodes. Freshly extracted and, therefore, immature CD4- DC exhibited a potent cytotoxic activity against a large panel of tumor cell lines as well as primary endothelial cells. The cytotoxic activity of immature CD4- DC required cell-to-cell contact and de novo protein expression. CD4- DC-mediated cell death resembled apoptosis, as evidenced by outer membrane phosphatidylserine exposure and nuclear fragmentation in target cells, but was caspase as well as Fas-associated death domain and receptor-interacting protein independent. Bcl-2 overexpression in target cells did not protect them against DC-mediated cell death. Immature CD4- DC phagocytosed efficiently apoptotic cells in vitro and, therefore, rapidly and specifically engulfed their victims following death induction. Maturation induced a dramatic down-regulation of the killing and phagocytic activities of CD4- DC. In contrast, CD4+ DC were both unable to kill target cells and to phagocytose apoptotic cells in vitro. Taken together, these data indicate that rat immature CD4- CD103+ DC mediate an unusual cytotoxic activity and can use this function to efficiently acquire Ag from live cells.
Trinité
Benjamin
B
Institut National de la Santé et de la Recherche Médicale Unité 643, Institut de Transplantation et de Recherche en Transplantation, Nantes University Hospital, Nantes, France.
Chauvin
Camille
C
Pêche
Hélène
H
Voisine
Cécile
C
Heslan
Michèle
M
Josien
Régis
R
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D017209:Apoptosis / Q000276:immunology*; D015704:CD4 Antigens / Q000378:metabolism*; D020169:Caspases / Q000502:physiology*; D002450:Cell Communication / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D039001:Integrin alpha Chains / Q000096:biosynthesis*; D019169:Jurkat Cells; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D014176:Protein Biosynthesis / Q000276:immunology; D011506:Proteins / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D015704:CD4 Antigens; C505533:FADD protein, human; C505535:Fadd protein, rat; D053200:Fas-Associated Death Domain Protein; D000949:Histocompatibility Antigens Class II; D039001:Integrin alpha Chains; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C091367:alpha E integrins; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D020169:Caspases