TRANCE, a tumor necrosis factor family member critical for CD40 ligand-independent T helper cell activation.
TRANCE, a tumor necrosis factor family member critical for CD40 ligand-independent T helper cell activation.
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DOI：
10.1084/jem.189.7.1025
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发表时间：
1999-04-05
期刊：
影响因子：
--
通讯作者：
Choi Y
中科院分区：
文献类型：
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作者：
Bachmann MF;Wong BR;Josien R;Steinman RM;Oxenius A;Choi Y
CD 40配体（CD 40 L）是肿瘤坏死因子（TNF）家族成员，在体内抗原特异性T细胞应答中起关键作用。在活化的CD 4 + T细胞上表达的CD 40 L刺激抗原呈递细胞如树突状细胞，导致共刺激分子的上调和体内CD 4 + T细胞引发所需的各种炎性细胞因子的产生。然而，用病毒攻击的CD 40 L或CD 40缺陷小鼠产生正常水平干扰素γ的保护性CD 4 + T细胞应答，表明CD 4 + T细胞引发的CD 40 L/CD 40非依赖性机制迄今尚未阐明。在这里，我们表明，CD 4 + T细胞对病毒感染的反应大大减少了CD 40缺陷小鼠的可溶性形式的TNF相关的激活诱导的细胞因子受体（TRANCE-R），以抑制另一个TNF家族成员，TRANCE的功能。因此，TRANCE/TRANCE-R相互作用提供了在不存在CD 40 L/CD 40的情况下病毒感染期间有效CD 4 + T细胞引发所需的共刺激。这些结果还表明，即使是由病毒感染诱导的有效炎症微环境也不足以在没有TNF家族（CD 40 L或TRANCE）提供的适当共刺激的情况下引发有效的CD 4 + T细胞引发。此外，数据表明TRANCE/TRANCE-R可能是免疫干预的新的重要靶点。
CD40 ligand (CD40L), a tumor necrosis factor (TNF) family member, plays a critical role in antigen-specific T cell responses in vivo. CD40L expressed on activated CD4+ T cells stimulates antigen-presenting cells such as dendritic cells, resulting in the upregulation of costimulatory molecules and the production of various inflammatory cytokines required for CD4+ T cell priming in vivo. However, CD40L- or CD40-deficient mice challenged with viruses mount protective CD4+ T cell responses that produce normal levels of interferon γ, suggesting a CD40L/CD40-independent mechanism of CD4+ T cell priming that to date has not been elucidated. Here we show that CD4+ T cell responses to viral infection were greatly diminished in CD40-deficient mice by administration of a soluble form of TNF-related activation-induced cytokine receptor (TRANCE-R) to inhibit the function of another TNF family member, TRANCE. Thus, the TRANCE/TRANCE-R interaction provides costimulation required for efficient CD4+ T cell priming during viral infection in the absence of CD40L/CD40. These results also indicate that not even the potent inflammatory microenvironment induced by viral infections is sufficient to elicit efficient CD4+ T cell priming without proper costimulation provided by the TNF family (CD40L or TRANCE). Moreover, the data suggest that TRANCE/TRANCE-R may be a novel and important target for immune intervention.