title: Selective addition of CXCR3(+) CCR4(-) CD4(+) Th1 cells enhances generation of cytotoxic T cells by dendritic cells in vitro.
abstract: Increasing importance is being given to the stimulation of Th1 response in cancer immunotherapy because its presence can shift the direction of adaptive immune responses toward protective immunity. Based on chemokine receptor expression, CXCR3(+) CCR4(-) CD4(+) T cells as Th1-type cells were investigated its capacity in monocyte-derived dendritic cell (DC) maturation and polarization, and induction of antigen specific cytotoxic T lymphocytes (CTL) in vitro. The levels of IL-4, IL-5 and IL-10 were decreased to the basal level compared with high production of IFN-gamma, TNF-alpha, and IL-2 in CXCR3+CCR4-CD4+ T cells stimulated with anti-CD3 and anti-CD28 antibodies. Co-incubation of activated CD4(+) or CXCR3(+) CCR4-CD4(+) T cells with DC (CD4(+/) DC or CXCR3(+) CD4(+/) DC, respectively) particularly up-regulated IL-12 and CD80 expression compared with DC matured with TNF-a and LPS (mDC). Although there was no significant difference between the effects of the CXCR3(+) CCR4(-) CD4(+) and CD4(+) T cells on DC phenotype expression, CXCR3(+) CD4(+/) DC in CTL culture were able to expand number of CD8(+) T cells and increased frequencies of IFN-gamma secreting cells and overall cytolytic activity against tumor antigen WT-1. These results demonstrated that the selective addition of CXCR3(+) CCR4(-) CD4(+) T cells to CTL cultures could enhance the induction of CTLs by DC in vitro, and implicated on a novel strategy for adoptive T cell therapy.
authors.affiliation: Department of Microbiology and Immunology College of Medicine, The Catholic University of Korea Seoul 137-701, Korea.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Yoon
authors.forename: Sun Ok
authors.initials: SO
authors.lastname: Yun
authors.forename: Jung Yong
authors.initials: JY
authors.lastname: Park
authors.forename: Hee Yeun
authors.initials: HY
authors.lastname: Won
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Kim
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Sohn
authors.forename: Hyun Il
authors.initials: HI
authors.lastname: Cho
authors.forename: Tai Gyu
authors.initials: TG
authors.lastname: Kim
mesh_terms: D015704:CD4 Antigens / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D054398:Receptors, CCR4 / Q000276:immunology*; D054367:Receptors, CXCR3 / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*
chemical_list: C515354:CCR4 protein, human; D015704:CD4 Antigens; C515187:CXCR3 protein, human; D016207:Cytokines; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D007371:Interferon-gamma