Full T-cell activation and function in teleosts require collaboration of first and co-stimulatory signals  

作　　者：Wei Liang Kang Li Haiyou Gao Kunming Li Jiansong Zhang Qian Zhang Xinying Jiao Jialong Yang Xiumei Wei 

机构地区：[1]State Key Laboratory of Estuarine and Coastal Research,School of Life Sciences,East China Normal University,Shanghai 200241,China [2]Laboratory for Marine Biology and Biotechnology,Qingdao National Laboratory for Marine Science and Technology,Qingdao,Shandong 266237,China

出　　处：《Zoological Research》2024年第1期13-24,共12页动物学研究（英文）

基　　金：supported by the National Key Research and Development Program(2022YFD2400804);National Natural Science Foundation of China(32022086,31972822);Natural Science Foundation of Shanghai(20ZR1417500)。

摘　　要：Mammalian T-cell responses require synergism between the first signal and co-stimulatory signal.However,whether and how dual signaling regulates the T-cell response in early vertebrates remains unknown.In the present study,we discovered that the Nile tilapia(Oreochromis niloticus)encodes key components of the LAT signalosome,namely,LAT,ITK,GRB2,VAV1,SLP-76,GADS,and PLC-γ1.These components are evolutionarily conserved,and CD3εmAb-induced T-cell activation markedly increased their expression.Additionally,at least ITK,GRB2,and VAV1 were found to interact with LAT for signalosome formation.Downstream of the first signal,the NF-κB,MAPK/ERK,and PI3K-AKT pathways were activated upon CD3εmAb stimulation.Furthermore,treatment of lymphocytes with CD28 mAbs triggered the AKT-mTORC1 pathway downstream of the co-stimulatory signal.Combined CD3εand CD28 mAb stimulation enhanced ERK1/2 and S6 phosphorylation and elevated NFAT1,c-Fos,IL-2,CD122,and CD44 expression,thereby signifying T-cell activation.Moreover,rather than relying on the first or co-stimulatory signal alone,both signals were required for T-cell proliferation.Full T-cell activation was accompanied by marked apoptosis and cytotoxic responses.These findings suggest that tilapia relies on dual signaling to maintain an optimal T-cell response,providing a novel perspective for understanding the evolution of the adaptive immune system.

关 键 词：Oreochromis niloticus CD3 CD28 T cells Adaptive immunity Evolution 

分 类 号：Q952.5[生物学—动物学]