Hideo Yagita

Juntendo University, Edo, Tōkyō, Japan

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Publications (2)10.49 Total impact

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    ABSTRACT: Dendritic cells (DCs) are the key antigen presenting cells not only for the priming of naïve T cells, but also for the induction and maintenance of peripheral T-cell tolerance. We have recently shown that cognate interactions between Foxp3(+) regulatory T cells and steady state DCs are crucial to maintain the tolerogenic potential of DCs. Using DIETER mice, which allow the induction of antigen presentation selectively on DCs without altering their maturation status, we show here that breakdown of CD8(+) T-cell tolerance, which ensues after depletion of suppressive CD4(+) T cells, is driven by a positive feedback loop in which auto-reactive CD8(+) T cells activate DCs via CD40. These data identify ligation of CD40 on DCs as a stimulus that promotes auto-reactive T-cell priming when regulatory T-cell suppression fails and suggest that feedback from auto-reactive T cells to DCs may contribute to the well-documented involvement of CD40 in many autoimmune diseases. This article is protected by copyright. All rights reserved.
    European Journal of Immunology 01/2014; · 4.97 Impact Factor
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    ABSTRACT: Radiotherapy is an important treatment for cancer. The main mode of action is thought to be the irreversible damage to tumor cell DNA, but there is evidence that irradiation mobilizes tumor-specific immunity, and recent studies showed that the efficacy of high-dose radiotherapy depends on the presence of CD8(+) T cells. We show in this study that the efficacy of radiotherapy given as a single, high dose (10 Gy) crucially depends on dendritic cells and CD8(+) T cells, whereas CD4(+) T cells or macrophages are dispensable. We show that local high-dose irradiation results in activation of tumor-associated dendritic cells that in turn support tumor-specific effector CD8(+) T cells, thus identifying the mechanism that underlies radiotherapy-induced mobilization of tumor-specific immunity. We propose that in the absence of irradiation, the activation status of dendritic cells rather than the amount of tumor-derived Ag is the bottleneck, which precludes efficient anti-tumor immunity.
    The Journal of Immunology 06/2012; 189(2):558-66. · 5.52 Impact Factor