TRAV7-2*02 Expressing CD8⁺ T Cells Are Responsible for Palladium Allergy.
TRAV7-2*02 Expressing CD8⁺ T Cells Are Responsible for Palladium Allergy.
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DOI：
10.3390/ijms18061162
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发表时间：
2017-05-31
影响因子：
5.6
通讯作者：
Ogasawara K
中科院分区：
文献类型：
--
作者：
Takeda Y;Suto Y;Ito K;Hashimoto W;Nishiya T;Ueda K;Narushima T;Takahashi T;Ogasawara K
虽然金属生物材料导致了生活质量的改善，但金属过敏，特别是对钯(PD)的过敏，导致最近过敏患者的数量增加。金属过敏是一种T细胞介导的迟发型超敏反应(DTH)，但致病T细胞亚群和特异性T细胞受体(TCR)尚未确定。因此，我们试图确定与PD过敏有关的致病T细胞。我们发现PD过敏小鼠激活的CD8+T细胞显著增加，TRAV(TCRαVariable)7-2*02链发生偏斜。过继转移实验表明，在体外培养的PD刺激的抗原提呈细胞(APC)在发生PD过敏的受体小鼠中起到记忆APC的作用，TRAV7-2*02的频率与常规PD过敏小鼠相同。相反，在主要组织相容性复合体I(MHC I)缺陷的PD-APC中，未观察到CD8+T细胞的增殖和TRAV7-2*02的增加。综上所述，我们揭示了表达TRAV7-2*02的CD8+T细胞是PD变态反应发生发展的致病T细胞。我们还在TRAV7-2*02/TRAJ(TCRα连接)22*01阳性细胞中鉴定了致病TCR的CDR3共有基序为CAAXSGSWQLIF。这些结果表明，特异性TCR为金属过敏的诊断和治疗提供了新的靶点。
While metallic biomaterials have led to an improvement in the quality of life, metal allergies, especially to palladium (Pd), has caused a recent increase in allergic patients. Metal allergy is known to be a T cell-mediated delayed-type hypersensitivity (DTH); however, the pathogenic T cell subsets and the specific T cell receptor (TCR) have not been identified. Therefore, we attempted to identify the pathogenic T cells responsible for Pd allergy. We found that activating CD8+ T cells significantly increased and that the TRAV (TCRα variable) 7-2*02 chain skewed in Pd allergic mice. Furthermore, adoptive transfer experiments revealed that in vitro-cultured Pd-stimulated antigen presenting cells (APCs) function as memory APCs with recipient mice developing Pd allergy and that the frequency of TRAV7-2*02 increases the same as conventional Pd allergic mice. In contrast, neither proliferation of CD8+ T cells nor increasing of TRAV7-2*02 was observed in major histocompatibility complex I (MHC I)-deficient Pd-APCs transferred to mice. Taken together, we revealed that TRAV7-2*02-expressing CD8+ T cells are the pathogenic T cells for the development of Pd allergy. We also identified the CDR3 consensus motif of pathogenic TCRs as CAAXSGSWQLIF in TRAV7-2*02/TRAJ (TCRα junction)22*01 positive cells. These results suggest that the specific TCRs represent novel targets for the development of diagnostics and treatments for metal allergy.