Andreasen S O, Christensen J P, Marker O, Thomsen A R
Institute of Medical Microbiology and Immunology, University of Copenhagen, The Panum Institute, 3C Blegdamsvej 2200, Copenhagen N, Denmark.
Int Immunol. 1999 Sep;11(9):1463-73. doi: 10.1093/intimm/11.9.1463.
In this report the significance of virus-induced non-specific T cell activation was re-evaluated using transgenic mice in which about half of the CD8(+) T cells expressed a TCR specific for amino acids 33-41 of lymphocytic choriomeningitis virus glycoprotein I. This allowed tracing of cells with known specificity and priming history in an environment also containing a normal heterogeneous CD8(+) population which served as an intrinsic control. Three parameters of T cell activation were analyzed: cell cycle progression, phenotypic conversion and cytolytic activity. Following injection of the IFN inducer poly(I:C), proliferation of memory (CD44(hi)) CD8(+) T cells but no phenotypic or functional activation was observed. Following injection of an unrelated virus [vesicular stomatitis virus (VSV)], naive TCR transgenic cells did not become significantly activated with respect to any of the parameters investigated. In contrast, memory TCR transgenic cells were found to proliferate extensively early after VSV infection (day 0-3), whereas limited proliferation was observed later (day 3-6) when proliferation of non-transgenic CD8(+) T cells is maximal. This aborted response did not result from anergy to TCR stimulation, as memory TCR transgenic cells proliferated vigorously upon stimulation with their nominal peptide. Despite the massive proliferation of memory cells observed early after VSV infection, no phenotypic or functional activation was observed. Together these findings indicate that both non-specific and antigen-specific signals contribute to the initial virus-induced proliferation of CD8(+) T cells, but for further proliferation and differentiation to take place, TCR-ligand interaction is required. The implications for maintenance of T cell memory is discussed.
在本报告中，利用转基因小鼠重新评估了病毒诱导的非特异性T细胞活化的意义，在这些转基因小鼠中，约一半的CD8(+) T细胞表达对淋巴细胞性脉络丛脑膜炎病毒糖蛋白I的氨基酸33 - 41具有特异性的TCR。这使得在一个也包含正常异质性CD8(+)群体作为内在对照的环境中，能够追踪具有已知特异性和启动历史的细胞。分析了T细胞活化的三个参数：细胞周期进程、表型转化和细胞溶解活性。注射IFN诱导剂聚肌胞苷酸（poly(I:C)）后，记忆性（CD44(hi)）CD8(+) T细胞增殖，但未观察到表型或功能活化。注射无关病毒[水疱性口炎病毒（VSV）]后，幼稚TCR转基因细胞在任何所研究的参数方面均未显著活化。相反，发现记忆性TCR转基因细胞在VSV感染后早期（第0 - 3天）大量增殖，而在后期（第3 - 6天）非转基因CD8(+) T细胞增殖达到最大值时观察到有限的增殖。这种中止的反应并非由于对TCR刺激的无反应性，因为记忆性TCR转基因细胞在用其名义肽刺激后强烈增殖。尽管在VSV感染后早期观察到记忆细胞大量增殖，但未观察到表型或功能活化。这些发现共同表明，非特异性和抗原特异性信号均有助于CD8(+) T细胞最初的病毒诱导增殖，但要发生进一步的增殖和分化，则需要TCR - 配体相互作用。讨论了对T细胞记忆维持的影响。
