Dendritic cells decreased the concomitant expanded Tregs and Tregs related IL-35 in cytokine-induced killer cells and increased their cytotoxicity against leukemia cells.
Regulatory T cells (Tregs) are potent immunosuppressive cells and essential for inducing immune tolerance. Recent studies have reported that Tregs and Tregs related cytokines can inhibit the antitumor activity of cytokine-induced killer (CIK) cells, but dendritic cells co-cultured CIK (DC-CIK) cells can be used for induction of a specific immune response by blocking of Tregs and TGF-β, IL-10. As a novel identified cytokine, IL-35 is specially produced by Tregs and plays an essential role in immune regulation. However, it remains unknown whether IL-35 roles in tumor immunotherapy mediated by CIK and DC-CIK cells. In this study, we cultured CIK and DC-CIK cells from the same healthy adult samples, and investigated their phenotype, proliferation, cytotoxic activity against leukemia cell lines K562 and NB4 by FCM and CCK-8, measured IL-35, TGF-β and IL-10 protein by ELISA, detected Foxp3, IL-35 and IL-35 receptor mRNA by Real-time PCR, respectively. We found Tregs and IL-35 concomitantly expanded by a time-dependent way during the generation of CIK cells, but DC significantly down-regulated the expression of them and simultaneously up-regulated the proliferation ability as well as cytotoxic activity of CIK cells against leukemia cell lines. Therefore, our data suggested that DC decreased concomitant expanded Tregs and Tregs related IL-35 in CIK cells and might contribute to improve their cytotoxicity against leukemia cells in vitro.
Department of Hematology, the Second Hospital of Anhui Medical University, and Hematology Research Center, Hefei, Anhui, People's Republic of China.
Ying
Y
Pan
Department of Hematology, the Second Hospital of Anhui Medical University, and Hematology Research Center, Hefei, Anhui, People's Republic of China.
Qianshan
Q
Tao
Department of Hematology, the Second Hospital of Anhui Medical University, and Hematology Research Center, Hefei, Anhui, People's Republic of China.
Huiping
H
Wang
Department of Hematology, the Second Hospital of Anhui Medical University, and Hematology Research Center, Hefei, Anhui, People's Republic of China.
Shudao
S
Xiong
Department of Hematology, the Second Hospital of Anhui Medical University, and Hematology Research Center, Hefei, Anhui, People's Republic of China.
Rui
R
Zhang
Department of Hematology, the Second Hospital of Anhui Medical University, and Hematology Research Center, Hefei, Anhui, People's Republic of China.
Tianping
T
Chen
Department of Hematology, the Second Hospital of Anhui Medical University, and Hematology Research Center, Hefei, Anhui, People's Republic of China.
Lili
L
Tao
Department of Hematology, the Second Hospital of Anhui Medical University, and Hematology Research Center, Hefei, Anhui, People's Republic of China.
Zhimin
Z
Zhai
D000328:Adult; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D055612:Cytokine-Induced Killer Cells / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000502:physiology*; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D020014:K562 Cells; D007938:Leukemia / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000378:metabolism / Q000502:physiology*
D007378:Interleukins; C532417:interleukin-35, human