Interferon producing killer dendritic cells (IKDC): A matter of controversy

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• 作者：Aizea Morales ; Carmen Ochoa ; Así ; s Palazó ; n ; Juan Dubrot ; Belé ; n Palencia ; Carlos Alfaro ; Natalia Suarez ; Ivá ; n Martí ; nez Forero ; Sandra Hervá ; s-Stubbs ; Ignacio Melero ; ^{imelero@unav.es}
• 关键词：Natural Killer ; Dendritic Cell ; Antigen presentation ; Interferon
• 刊名：Inmunolog¨ªa
• 出版年：2010
• 出版时间：January-March 2010
• 年：2010
• 卷：29
• 期：1
• 页码：50-55
• 全文大小：97 K

文摘

Division of labour among cells of the immune system is a prevailing theme in the orchestration of immune responses. Contrary to this paradigm, a particular leukocyte population in the mouse seems to be equipped with the ability to kill transformed and virally infected cells and with the capability to mediate antigen processing and presentation to T cells. Those two functions are classically ascribed separately to Natural Killer (NK) cells and Dendritic cells (DC). IKDC (interferon-producing killer dendritic cell) were defined in mice as cells expressing CD11c, although to a lesser extent than conventional DCs (cDCs), while coexpressing B220, NK1.1, CD49b (VLA-2) and MHC Class II molecules. Absence of CD3, CD19 and Gr1(Ly49c) expression also featured this minor subset upon multicolour FACS characterization. These cells kill a variety tumor cell lines in a TRAIL-dependent fashion. Furthermore, IKDC produce high amounts of Interferon (IFN) gamma (IFN-¦Ã) and type I IFN upon activation by combined interleukins (IL-18, IL-2, IL-12 or IL-15), tumor cells, or TLR-9 nucleotide agonists. Importantly, these cells may present antigen to prime CD4 and CD8 T cells. The discovery of this subset in mice was reported in two back to back articles published in Nature Medicine in 2006, along with a comment that highlighted how such a cell may provide the ability to kill cells in an innate fashion while starting T-cell adaptive immunity by means of cross-presentation of antigens collected from the apoptotic remains of their victim cells. However, two years later three articles in a single issue of the Journal of Experimental Medicine contended that such a population did not exist and that IKDC were actually nothing more than activated NK cells. The arguments were based on the inability of IKDC to present antigen and prime T cells, and on their dependency on IL-15 for differentiation and survival. Later on, the groups that first described IKDC have provided evidence that such a subpopulation can mediate antigen presentation and have also stressed several characteristics that discriminate activated NK cells and IKDC. The reasons for some of these experimental discrepancies are obscure. Yet, the core of the controversy is to establish wether the hybrid abilities proposed for such minor leukocyte population are relevant to physiology, pathology or therapy. To date, no equivalent population has been described in human lymphoid tissues.