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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.
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Submitted March 3, 2008
Accepted July 13, 2008
Dendritic cells mediate the induction of polyfunctional human IL17 producing cells (Th17-1 cells) enriched in the bone marrow of myeloma patients
Kavita M Dhodapkar*, Scott Barbuto, Phillip Matthews, Anjli Kukreja, Amitabha Mazumder, David Vesole, Sundar Jagannath, and Madhav V Dhodapkar
Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY, United States
Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY, United States
Myeloma Center, St. Vincent's Cancer Center, New York, NY, United States
Section of Hematology, Yale University, New Haven, CT, United States
* Corresponding author; email: dhodapk{at}rockefeller.edu.
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 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, wherein tumors are infiltrated by DCs, Th17 cells are enriched in the bone marrow relative to circulation. Bone marrow from myeloma patients contains higher proportion of Th17-1 cells compared to the marrow in preneoplastic gammopathy (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.
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