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Blood, 1 January 2005, Vol. 105, No. 1, pp. 266-273.
Prepublished online as a Blood First Edition Paper on August 26, 2004; DOI 10.1182/blood-2004-06-2492.
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Submitted June 30, 2004
Accepted August 16, 2004
Mature myeloid dendritic cell subsets have distinct roles for activation and viability of circulating human natural killer cells
Christian Munz*, Tao Dao, Guido Ferlazzo, Maria A de Cos, Kiera Goodman, and James W Young
Laboratory of Viral Immunobiology, The Rockefeller University, New York, NY, USA; Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY, USA
Laboratory of Cellular Immunobiology, Memorial Sloan-Kettering Cancer Center and Weill Medical College of Cornell University, New York, NY, USA
Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY, USA; Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY, USA
Laboratory of Cellular Immunobiology, Memorial Sloan-Kettering Cancer Center and Weill Medical College of Cornell University, New York, NY, USA; Allogeneic Bone Marrow Transplant and Clinical Immunology Services, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Medical College of Cornell University, New York, NY, USA
* Corresponding author; email: munzc{at}rockefeller.edu.
Natural killer (NK) cells are important effectors of innate immunity. In contrast to many studies of IL-2 activated NK cells, the physiologic requirements for stimulating resting NK cells have only recently received attention. Given the emerging variety of DC types and their division of labor for stimulating immunity, we compared the capacity of moDCs with that of CD34+ hematopoietic progenitor cell (HPC)-derived dermal-interstitial DCs (DDC-IDCs) and Langerhans cells (LCs) to stimulate resting NK cells. MoDCs, and to a lesser extent CD34+ HPC-derived DDC-IDCs, directly stimulate NK cell proliferation, CD56 upregulation, and cytotoxicity. LCs, on the contrary, require exogenous IL-2 or IL-12 to activate NK cells; but they can maintain resting NK cell viability and sustain NK cell proliferation induced by moDCs. LCs do not secrete bioactive IL-12p70, but do produce significantly higher concentrations of IL-15 and IL-18 than either of the other two DC types. Despite secretion of IL-15, LCs lack IL-15R-alpha for surface presentation of IL-15. This together with the deficiency of IL-12p70 undermines any direct NK cell activation by LCs. Hence the principal myeloid DCs differ in critical ways for the stimulation of NK and T lymphocytes and could be used or targeted accordingly in DC-based immunotherapies.
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