Selective addition of CXCR3 super(+)CCR4 super(-)CD 4 super(+) Th1 cells enhances generation of cytotoxic T cells by dendritic cells in vitro

• Published in: Experimental & molecular medicine Vol. 41; no. 3; pp. 161 - 170
• Main Authors: Yoon, Sung Hee, Yun, Sun Ok, Park, Jung Yong, Won, Hee Yeun, Kim, Eun-Kyung, Sohn, Hyun-Jung, Cho, Hyun-Il, Kim, Tai-Gyu
• Format: Journal Article
• Language: English
• Published: 01.03.2009
• ISSN: 1226-3613
• DOI: 10.3858/emm.2009.41.3.019

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 super(+)CCR4 super(-)CD 4 super(+) 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 super(+)CCR4 super(-)CD 4 super(+) T cells stimulated with anti-CD3 and anti-CD28 antibodies. Co-incubation of activated CD4 super(+) or CXCR3 super(+)CCR4 super(-)CD 4 super(+) T cells with DC (CD4 super(+)/DC or CXCR3 super(+)CD4 super(+)/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 super(+)CCR4 super(-)CD 4 super(+) and CD4 super(+) T cells on DC phenotype expression, CXCR3 super(+)CD4 super(+)/DC in CTL culture were able to expand number of CD8 super(+) 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 super(+)CCR4 super(-)CD 4 super(+) 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.