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Blood, 1 October 2008, Vol. 112, No. 7, pp. 2878-2885. Prepublished online as a Blood First Edition Paper on July 30, 2008; DOI 10.1182/blood-2008-03-143222. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-03-143222v1 112/7/2878    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dhodapkar, K. M. Articles by Dhodapkar, M. V. Search for Related Content PubMed PubMed Citation Articles by Dhodapkar, K. M. Articles by Dhodapkar, M. V. Related Collections Immunobiology Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Dendritic cells mediate the induction of polyfunctional human IL17-producing cells (Th17-1 cells) enriched in the bone marrow of patients with myeloma Kavita M. Dhodapkar1, Scott Barbuto1, Phillip Matthews2, Anjli Kukreja2, Amitabha Mazumder3, David Vesole3, Sundar Jagannath3, and Madhav V. Dhodapkar2,4,5 1 Laboratory of Cellular Physiology and Immunology and 2 Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY; 3 St Vincent's Cancer Center, New York, NY; 4 Section of Hematology, Yale University, New Haven, CT; and 5 Program in Hematologic Malignancies, Yale Cancer Center, New Haven, CT IL17-producing (Th17) cells are a distinct lineage of T helper cells that regulate immunity and inflammation. The role of antigen-presenting cells in the induction of Th17 cells in humans remains to be fully defined. Here, we show that human dendritic cells (DCs) are efficient inducers of Th17 cells in culture, including antigen-specific Th17 cells. Although most freshly isolated circulating human Th17 cells secrete IL17 alone or with IL2, those induced by DCs are polyfunctional and coexpress IL17 and IFN (Th17-1 cells). The capacity of DCs to expand Th17-1 cells is enhanced upon DC maturation, and mature DCs are superior to monocytes for the expansion of autologous Th17 cells. In myeloma, where tumors are infiltrated by DCs, Th17 cells are enriched in the bone marrow relative to circulation. Bone marrow from patients with myeloma contains a higher proportion of Th17-1 cells compared with the marrow in preneoplastic gammopathy (monoclonal gammopathy of undetermined significance [MGUS]). Uptake of apoptotic but not necrotic myeloma tumor cells by DCs leads to enhanced induction of Th17-1 cells. These data demonstrate the capacity of DCs to induce expansion of polyfunctional IL17-producing T cells in humans, and suggest a role for DCs in the enrichment of Th17-1 cells in the tumor bed. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Kukreja, S. Radfar, B.-H. Sun, K. Insogna, and M. V. Dhodapkar Dominant role of CD47-thrombospondin-1 interactions in myeloma-induced fusion of human dendritic cells: implications for bone disease Blood, October 15, 2009; 114(16): 3413 - 3421. [Abstract] [Full Text] [PDF] G. Murugaiyan and B. Saha Protumor vs Antitumor Functions of IL-17 J. Immunol., October 1, 2009; 183(7): 4169 - 4175. [Abstract] [Full Text] [PDF] E. Gounaris, N. R. Blatner, K. Dennis, F. Magnusson, M. F. Gurish, T. B. Strom, P. Beckhove, F. Gounari, and K. Khazaie T-Regulatory Cells Shift from a Protective Anti-Inflammatory to a Cancer-Promoting Proinflammatory Phenotype in Polyposis Cancer Res., July 1, 2009; 69(13): 5490 - 5497. [Abstract] [Full Text] [PDF]

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