IFN-γ inhibits presentation of a tumor/self peptide by CD8α- dendritic cells via potentiation of the CD8α+ subset
IFN-γ inhibits presentation of a tumor/self peptide by CD8α- dendritic cells via potentiation of the CD8α+ subset
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DOI：
10.4049/jimmunol.165.3.1357
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发表时间：
2000-08-01
影响因子：
4.4
通讯作者：
Puccetti, P
中科院分区：
文献类型：
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作者：
Grohmann, U;Bianchi, R;Puccetti, P
利用肿瘤/自身肽呈递的体内模型诱导i类限制性皮肤试验反应性，我们之前已经证明，在DBA/2小鼠中，少数CD8（+）树突状细胞（DC）负调控肽负载CD8(-) DC对T细胞反应性的诱导。然而，当两种类型的DC共转移到受体宿主中时，CD8（-）部分可以被IL-12引物以克服CD8（+）亚群的抑制。我们在这里报道，CD8(+) DC暴露于ifn - γ大大增强了它们对其他亚群Ag呈递的抑制活性，阻断了il -12处理的CD8(-) DC克服抑制的能力。相比之下，ifn - γ对后者细胞的APC功能没有直接影响，也不会干扰IL-12信号传导。ifn - γ在CD8(+) DC中引发的负调控作用似乎与体内色氨酸代谢的干扰有关。通过色氨酸消耗影响T细胞应答，ifn - γ作用于CD8(+) DC，因此可能有助于调节对CD8（-）亚群呈递的肿瘤/自身肽的免疫。
Using an in vivo model of tumor/self peptide presentation for induction of class I-restricted skin test reactivity, we have previously shown that a minority population of CD8(+) dendritic cells (DC) negatively regulates the induction of T cell reactivity by peptide-loaded CD8(-) DC in DBA/2 mice. However, the CD8(-) fraction can be primed by IL-12 to overcome inhibition by the CD8(+) subset when the two types of DC are cotransferred into recipient hosts. We report here that exposure of CD8(+) DC to IFN-gamma greatly enhances their inhibitory activity on Ag presentation by the other subset, blocking the ability of IL-12-treated CD8(-) DC to overcome suppression. In contrast, IFN-gamma has no direct effects on the APC function of the latter cells and does not interfere with IL-12 signaling. The negative regulatory effect triggered by IFN-gamma in CD8(+) DC appears to involve interference with tryptophan metabolism in vivo. Through tryptophan depletion affecting T cell responses, IFN-gamma acting on CD8(+) DC may thus contribute to regulation of immunity to tumor/self peptides presented by the CD8(-) subset.