Inoue Shin-Ichi, Niikura Mamoru, Asahi Hiroko, Iwakura Yoichiro, Kawakami Yasushi, Kobayashi Fumie
Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan.
Research Institute for Biological Sciences, Tokyo University of Science, Chiba, Japan.
Eur J Immunol. 2017 Apr;47(4):685-691. doi: 10.1002/eji.201646699. Epub 2017 Jan 11.
γδ T cells play a crucial role in controlling malaria parasites. Dendritic cell (DC) activation via CD40 ligand (CD40L)-CD40 signaling by γδ T cells induces protective immunity against the blood-stage Plasmodium berghei XAT (PbXAT) parasites in mice. However, it is unknown which γδ T-cell subset has an effector role and is required to control the Plasmodium infection. Here, using antibodies to deplete TCR Vγ1 cells, we saw that Vγ1 γδ T cells were important for the control of PbXAT infection. Splenic Vγ1 γδ T cells preferentially expand and express CD40L, and both Vγ1 and Vγ4 γδ T cells produce IFN-γ during infection. Although expression of CD40L on Vγ1 γδ T cells is maintained during infection, the IFN-γ positivity of Vγ1 γδ T cells is reduced in late-phase infection due to γδ T-cell dysfunction. In Plasmodium-infected IFN-γ signaling-deficient mice, DC activation is reduced, resulting in the suppression of γδ T-cell dysfunction and the dampening of γδ T-cell expansion in the late phase of infection. Our data suggest that Vγ1 γδ T cells represent a major subset responding to PbXAT infection and that the Vγ1 γδ T-cell response is dependent on IFN-γ-activated DCs.
γδ T细胞在控制疟原虫方面发挥着关键作用。γδ T细胞通过CD40配体（CD40L）-CD40信号传导激活树突状细胞（DC），可诱导小鼠对血液期伯氏疟原虫XAT（PbXAT）寄生虫产生保护性免疫。然而，尚不清楚哪个γδ T细胞亚群具有效应作用且是控制疟原虫感染所必需的。在这里，我们使用抗体耗尽TCR Vγ1细胞，发现Vγ1 γδ T细胞对控制PbXAT感染很重要。脾脏Vγ1 γδ T细胞优先扩增并表达CD40L，并且在感染期间Vγ1和Vγ4 γδ T细胞均产生IFN-γ。尽管在感染期间Vγ1 γδ T细胞上CD40L的表达得以维持，但由于γδ T细胞功能障碍，Vγ1 γδ T细胞在感染后期的IFN-γ阳性率降低。在感染疟原虫的IFN-γ信号缺陷小鼠中，DC激活减少，导致γδ T细胞功能障碍受到抑制，并且在感染后期γδ T细胞扩增受到抑制。我们的数据表明，Vγ1 γδ T细胞是对PbXAT感染作出反应的主要亚群，并且Vγ1 γδ T细胞反应依赖于IFN-γ激活的DC。
