Abstract：
T cell activation is a multifaceted process that depends on the activation of the T cell receptor (TCR). However, other coreceptors are also strictly necessary to provide co-signals and modulate the immune response. However, to date, most of these coreceptors are unknown in fish or their information is very limited. Therefore, in this work, we have identified the cytotoxic and regulatory T cell molecule, CRTAM, and its ligand, the cell adhesion molecule 1, CADM1, in European seabass (Dicentrarchus labrax) and gilthead seabream (Sparus aurata); and evaluated their transcriptional levels. Both putative proteins showed the canonical architecture observed in mammals, where CRTAM exhibited two immunoglobulin domains and CADM1, both the a and b forms, exhibited three of these domains. In addition, phylogeny and synteny analyses showed their conservation throughout vertebrate evolution. We found constitutive expression of all three genes, with crtam and cadm1a being predominant in immune tissues such as spleen, thymus and head-kidney (HK), while cadm1b expression was more limited to the brain. In vitro, only the T cell mitogen phytohemagglutinin (PHA) up-regulated the transcription of crtam and cadm1a in HK leucocytes. Nodavirus (NNV) infection elicited an up-regulation of crtam and cadm1a in brain and HK, appearing earlier in seabream than in seabass, which could explain the resistance of seabream to the development of nodavirus disease. In addition, they are up-regulated during the innate cell-mediated cytotoxic response in seabream but not in seabass. Altogether, our data seem to indicate that CRTAM is more related to the innate cytotoxicity in seabream and more in the specific and T cell-mediated cytotoxicity in seabass. Our results highlight the importance of CRTAM and CADM1 as important molecules in the activation of T lymphocytes in seabass and seabream, but further studies are needed.
摘要：
T细胞活化是取决于T细胞受体(TCR)活化的多方面进程。然而,其他共受体也是提供共信号和调节免疫应答所必需的。然而,到目前为止,这些共受体中的大多数在鱼类中是未知的，或者它们的信息非常有限。因此,在这项工作中，我们已经确定了细胞毒性和调节性T细胞分子，CRTAM,和它的配体，在欧洲鲈鱼（Dicentrarchuslabrax）和金头鱼（Sparusaurata）中的细胞粘附分子1CADM1；并评估了它们的转录水平。两种推定的蛋白质都显示了在哺乳动物中观察到的规范结构，其中CRTAM表现出两个免疫球蛋白结构域和CADM1，都是a和b形式，展示了其中三个领域。此外,系统发育和同种学分析显示它们在整个脊椎动物进化中的保守性。我们发现所有三个基因的组成型表达，crtam和cadm1a在免疫组织如脾脏中占主导地位，胸腺和头肾(香港)，而cadm1b的表达更局限于大脑。体外，只有T细胞有丝分裂原植物血凝素（PHA）上调HK白细胞中crtam和cadm1a的转录。诺达病毒（NNV）感染引起大脑和HK中crtam和cadm1a的上调，在seabream中出现得比在seabass中更早，这可以解释河豚对夜曲病毒病发展的抗性。此外,他们是上调的先天细胞介导的细胞毒性反应期间，在sebream，而不是在sebass。总之,我们的数据似乎表明CRTAM更多地与沙鼠的先天细胞毒性相关,而更多地与沙鼠的特异性和T细胞介导的细胞毒性相关.我们的研究结果强调了CRTAM和CADM1作为重要分子在海底和海底T淋巴细胞活化中的重要性，但还需要进一步的研究。
