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The Journal of Immunology, 2005, 175: 2408-2417.
Copyright © 2005 by The American Association of Immunologists

Immature CD4–CD103+ Rat Dendritic Cells Induce Rapid Caspase-Independent Apoptosis-Like Cell Death in Various Tumor and Nontumor Cells and Phagocytose Their Victims1

Benjamin Trinité2,3, Camille Chauvin2, Hélène Pêche4, Cécile Voisine5, Michèle Heslan and Régis Josien6

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

We previously reported the characterization of a MHC class IIlowCD4–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.




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