Full T-cell activation and function in teleosts require collaboration of first and co-stimulatory signalsOACSTPCD
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.
Wei Liang;Kang Li;Haiyou Gao;Kunming Li;Jiansong Zhang;Qian Zhang;Xinying Jiao;Jialong Yang;Xiumei Wei
State Key Laboratory of Estuarine and Coastal Research,School of Life Sciences,East China Normal University,Shanghai 200241,ChinaState Key Laboratory of Estuarine and Coastal Research,School of Life Sciences,East China Normal University,Shanghai 200241,ChinaState Key Laboratory of Estuarine and Coastal Research,School of Life Sciences,East China Normal University,Shanghai 200241,ChinaState Key Laboratory of Estuarine and Coastal Research,School of Life Sciences,East China Normal University,Shanghai 200241,ChinaState Key Laboratory of Estuarine and Coastal Research,School of Life Sciences,East China Normal University,Shanghai 200241,ChinaState Key Laboratory of Estuarine and Coastal Research,School of Life Sciences,East China Normal University,Shanghai 200241,ChinaState Key Laboratory of Estuarine and Coastal Research,School of Life Sciences,East China Normal University,Shanghai 200241,ChinaState Key Laboratory of Estuarine and Coastal Research,School of Life Sciences,East China Normal University,Shanghai 200241,China Laboratory for Marine Biology and Biotechnology,Qingdao National Laboratory for Marine Science and Technology,Qingdao,Shandong 266237,ChinaState Key Laboratory of Estuarine and Coastal Research,School of Life Sciences,East China Normal University,Shanghai 200241,China
生物学
Oreochromis niloticusCD3CD28T cellsAdaptive immunityEvolution
《Zoological Research》 2024 (1)
P.13-24,12
supported by the National Key Research and Development Program(2022YFD2400804)National Natural Science Foundation of China(32022086,31972822)Natural Science Foundation of Shanghai(20ZR1417500)。
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