Li Xinran, Lai Guolong, Lin Yan, Liu Sichang, Bao Wenbing, Zhang Wenxuan, Huang Li, Shao Guangming, Chen Shihao, Ding Yang, Chen Xinhua
State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Fish Shellfish Immunol. 2025 Oct;165:110560. doi: 10.1016/j.fsi.2025.110560. Epub 2025 Jul 9.
CD4 T cells, also known as helper T (Th) cells, are crucial regulators of the adaptive immune system, orchestrating and coordinating immune responses that protect the host against a broad spectrum of pathogenic threats. Two CD4 co-receptor genes, cd4-1 and cd4-2, have been identified in teleost species, including the large yellow croaker Larimichthys crocea. In this study, we developed a monoclonal antibody (mAb) that specifically recognizes croaker CD4-2, enabling the identification and characterization of CD4-2 T lymphocytes. Croaker CD4-2 T cells were found predominantly distributed across both systemic and mucosal immune tissues, with the exception of peripheral blood, and were notably more abundant than IgM B cells in the liver, gut, head kidney (HK) and gills. Moreover, elevated transcription levels of ifng, il2, il17a/f3, and il6 in sorted HK CD4-2 T cells suggest their potential for functional differentiation into distinct Th lineages. Functional studies demonstrated that CD4-2 T cells in the HK and spleen exhibited robust proliferative responses upon in vitro stimulation with T cell mitogens, including Phytohemagglutinin-L and Concanavalin A. More importantly, following infection with the protozoan parasite Cryptocaryon irritans, pronounced proliferations of CD4-2 T cells were observed in the HK, spleen and gills, whereas the cellular expansion and activation were detected exclusively in the spleen, underscoring the pivotal role of the spleen in the induction and activation of CD4-2 T cells in large yellow croaker. This study provides an in-depth characterization of CD4-2 T cells in large yellow croaker and highlights their critical role in immune activation and anti-parasitic defense, offering valuable insights into their potential applications in immunological research and disease control in aquaculture.
CD4 T细胞，也被称为辅助性T（Th）细胞，是适应性免疫系统的关键调节因子，协调和统筹免疫反应，保护宿主抵御多种致病威胁。在硬骨鱼物种中，包括大黄鱼（Larimichthys crocea），已鉴定出两个CD4共受体基因，即cd4-1和cd4-2。在本研究中，我们开发了一种特异性识别大黄鱼CD4-2的单克隆抗体（mAb），从而能够鉴定和表征CD4-2 T淋巴细胞。发现大黄鱼CD4-2 T细胞主要分布于全身和黏膜免疫组织中，但外周血除外，并且在肝脏、肠道、头肾（HK）和鳃中明显比IgM B细胞丰富。此外，分选的HK CD4-2 T细胞中ifng、il2、il17a/f3和il6的转录水平升高，表明它们具有分化为不同Th谱系的功能潜力。功能研究表明，HK和脾脏中的CD4-2 T细胞在用T细胞有丝分裂原（包括植物血凝素-L和刀豆球蛋白A）进行体外刺激后表现出强劲的增殖反应。更重要的是，在用原生动物寄生虫刺激隐核虫感染后，在HK、脾脏和鳃中观察到CD4-2 T细胞明显增殖，而细胞扩增和激活仅在脾脏中检测到，这突出了脾脏在大黄鱼CD4-2 T细胞诱导和激活中的关键作用。本研究深入表征了大黄鱼中的CD4-2 T细胞，并强调了它们在免疫激活和抗寄生虫防御中的关键作用，为其在水产养殖免疫研究和疾病控制中的潜在应用提供了有价值的见解。
