Induction of CML28-specific cytotoxic T cell responses using co-transfected dendritic cells with CML28 DNA vaccine and SOCS1 small interfering RNA expression vector.
CML28 is an attractive target for antigen-specific immunotherapy. SOCS1 represents an inhibitory control mechanism for DC antigen presentation and the magnitude of adaptive immunity. In this study, we evaluated the potential for inducing CML28-specific cytotoxic T lymphocytes (CTL) responses by dendritic cells (DCs)-based vaccination. We constructed a CML28 DNA vaccine and a SOCS1 siRNA vector and then cotransfect monocyte-derived DCs. Flow cytometry analysis showed gene silencing of SOCS1 resulted in higher expressions of costimulative moleculars in DCs. Mixed lymphocyte reaction (MLR) indicated downregulation of SOCS1 stronger capability to stimulate proliferation of responder cell in DCs. The CTL assay revealed transfected DCs effectively induced autologous CML28-specific CTL responses and the lytic activities induced by SOCS1-silenced DCs were significantly higher compared with those induced by SOCS1-expressing DCs. These results in our study indicates gene silencing of SOCS1 remarkably enhanced the cytotoxicity efficiency of CML28 DNA vaccine in DCs.
Zhou
Hongsheng
H
Department of Hematology, Tongji Hospital, Tongji Medical College of Huazhong Science and Technology University, Wuhan, China.
Zhang
Donghua
D
Wang
Yaya
Y
Dai
Ming
M
Zhang
Lu
L
Liu
Wenli
W
Liu
Dan
D
Tan
Huo
H
Huang
Zhenqian
Z
D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology*; D000954:Antigens, Surface / Q000235:genetics* / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005095:Exoribonucleases / Q000235:genetics* / Q000276:immunology*; D063326:Exosome Multienzyme Ribonuclease Complex; D020868:Gene Silencing; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014162:Transfection / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage*
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; C467564:EXOSC5 protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D019444:Vaccines, DNA; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex