Rapid production of TNF-α following TCR engagement of naive CD8 T cells
Rapid production of TNF-α following TCR engagement of naive CD8 T cells
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DOI：
10.4049/jimmunol.175.8.5043
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发表时间：
2005-10-15
影响因子：
4.4
通讯作者：
Welsh, RM
中科院分区：
文献类型：
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作者：
Brehm, MA;Daniels, KA;Welsh, RM
初始CD8 T细胞在与TCR结合后获得效应功能被认为是顺序发生的，只有在分裂开始后才能获得完整的功能。我们发现初始CD8 T细胞能够在TCR参与后立即发挥效应功能，这刺激了tnf - α的快速产生。用抗cd3 epsilon单抗刺激具有不同遗传背景的幼年小鼠的脾细胞，可在5小时内使幼年CD8 T细胞显著产生tnf - α。此外，幼年淋巴细胞性脉络脑膜炎病毒特异性tcr转基因CD8 T细胞在其同源肽配体或病毒感染细胞刺激下，早在刺激后2小时就产生tnf - α，并在4小时达到峰值。幼年CD8 T细胞既产生膜结合型tnf - α，也产生可溶性tnf - α。在初始CD8 T细胞和载银树突状细胞初次相遇时，干扰tnf - α活性改变了APC的成熟特征，降低了APC群体的整体生存能力。这些发现表明，在TCR接触后，初始CD8 T细胞立即产生tnf - α，可能在发生Ag呈递的局部环境中产生未被认识到的影响，并可能影响免疫反应的发展。
The acquisition of effector functions by naive CD8 T cells following TCR engagement is thought to occur sequentially with full functionality being gained only after the initiation of division. We show that naive CD8 T cells are capable of immediate effector function following TCR engagement, which stimulates the rapid production of TNF-alpha. Stimulation of splenocytes from naive mice of differing genetic backgrounds with anti-CD3 epsilon mAb resulted in significant production of TNF-alpha by naive CD8 T cells within 5 h. Moreover, naive lymphocytic choriomeningitis virus-specific TCR-transgenic CD8 T cells stimulated with either their cognate peptide ligand or virus-infected cells produced TNF-alpha as early as 2 h poststimulation, with production peaking by 4 h. Naive CD8 T cells produced both membrane-bound and soluble TNF-alpha. Interfering with TNF-alpha activity during the initial encounter between naive CD8 T cells and Ag loaded dendritic cells altered the maturation profile of the APC and diminished the overall viability of the APC population. These findings suggest that production of TNF-alpha by naive CD8 T cells immediately after TCR engagement may have an unappreciated impact within the local environment where Ag presentation is occurring and potentially influence the development of immune responses.