Han Wanda G H, Schuurhuis Danita H, Fu Nathalie, Camps Marcel, van Duivenvoorde Leonie M, Louis-Plence Pascale, Franken Kees L M C, Huizinga Tom W J, Melief Cornelis J M, Toes René E M, Ossendorp Ferry
Department of Rheumatology, Leiden University Medical Center, The Netherlands.
Eur J Immunol. 2009 Jul;39(7):1765-73. doi: 10.1002/eji.200838842.
CD4(+) T cells are important for CD8(+) T-cell priming by providing cognate signals for DC maturation. We analyzed the capacity of CD4(+) T cells to influence CD8(+) T-cell responses induced by activated DC. Surprisingly, mice depleted for CD4(+) cells were able to generate stronger antigen-specific CD8(+) T-cell responses after DC vaccination than non-depleted mice. The same observation was made when mice were vaccinated with MHC class II(-/-) DC, indicating the presence of a MHC class II-dependent CD4(+) T-cell population inhibiting CD8(+) T-cell responses. Recently we described the expansion of DX5(+)CD4(+) T cells, a T-cell population displaying immune regulatory properties, upon vaccination with DC. Intriguingly, we now observe an inverse correlation between CD8(+) T-cell induction and expansion of DX5(+)CD4(+) T cells as the latter cells did not expand after vaccination with MHC class II(-/-) DC. In vitro, DX5(+)CD4(+) T cells were able to limit proliferation, modulate cytokine production and induce Foxp3(+) expression in OVA-specific CD8(+) T cells. Together, our data show an inhibitory role of CD4(+) T cells on the induction of CD8(+) T-cell responses by activated DC and indicate the involvement of DX5(+)CD4(+), but not CD4(+)CD25(+), T cells in this process.
CD4(+) T细胞通过为树突状细胞（DC）成熟提供同源信号，对CD8(+) T细胞的致敏起重要作用。我们分析了CD4(+) T细胞影响活化DC诱导的CD8(+) T细胞应答的能力。令人惊讶的是，CD4(+)细胞耗竭的小鼠在DC疫苗接种后比未耗竭的小鼠能够产生更强的抗原特异性CD8(+) T细胞应答。当用II类主要组织相容性复合体（MHC）缺陷的DC给小鼠接种疫苗时，也得到了相同的观察结果，这表明存在一个依赖II类MHC的CD4(+) T细胞群体抑制CD8(+) T细胞应答。最近我们描述了在用DC接种疫苗后，DX5(+)CD4(+) T细胞（一种具有免疫调节特性的T细胞群体）的扩增。有趣的是，我们现在观察到CD8(+) T细胞诱导与DX5(+)CD4(+) T细胞扩增之间呈负相关，因为在用II类MHC缺陷的DC接种疫苗后，后一种细胞没有扩增。在体外，DX5(+)CD4(+) T细胞能够限制增殖、调节细胞因子产生并在卵清蛋白特异性CD8(+) T细胞中诱导Foxp3(+)表达。总之，我们的数据显示CD4(+) T细胞对活化DC诱导的CD8(+) T细胞应答具有抑制作用，并表明DX5(+)CD4(+)而非CD4(+)CD25(+) T细胞参与了这一过程。
