Exp Mol Med.  2009 Mar;41(3):161-170. 10.3858/emm.2009.41.3.019.

Selective addition of CXCR3+CCR4-CD4+ Th1 cells enhances generation of cytotoxic T cells by dendritic cells in vitro

• Yoon SH
• Yun SO
• Park JY
• Won HY
• Kim EK
• Sohn HJ
• Cho HI
• Kim TG

• KMID: 1123463
• DOI: http://doi.org/10.3858/emm.2009.41.3.019

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-alpha 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.

Keyword

adoptive transfer; antigens, differentiation; dendritic cells; immunotherapy, adoptive; maturation; receptors, CCR4; receptors, CXCR3; T lymphocytes, cytotoxic; Th1 cells; Th2 cells

MeSH Terms

Antigens, CD4/*immunology
Cell Line
Cells, Cultured
Cytokines/immunology
Cytotoxicity, Immunologic
Dendritic Cells/cytology/*immunology
Humans
Interferon-gamma/biosynthesis
Receptors, CCR4/*immunology
Receptors, CXCR3/*immunology
T-Lymphocytes, Cytotoxic/*cytology/immunology
Th1 Cells/*immunology