Busch D H, Pilip I, Pamer E G
Section of Infectious Diseases and the Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
J Exp Med. 1998 Jul 6;188(1):61-70. doi: 10.1084/jem.188.1.61.
The mechanisms underlying the genesis and maintenance of T cell memory remain unclear. In this study, we examined the evolution of a complex, antigen-specific T cell population during the transition from primary effector to memory T cells after Listeria monocytogenes infection. T cell populations specific for listeriolysin O (LLO)91-99, the immunodominant epitope recognized by H2-Kd-restricted T lymphocytes, were directly identified in immune spleens using tetrameric H2-Kd-epitope complexes. The T cell receptor (TCR) Vbeta repertoire of specific T cells was determined by direct, ex vivo staining with a panel of mAbs. We demonstrate that LLO91-99-specific, primary effector T cell populations have a diverse TCR Vbeta repertoire. Analyses of memory T cell populations demonstrated similar TCR diversity. Furthermore, experiments with individual mice demonstrated that primary effector and memory T cells have indistinguishable TCR repertoires. Remarkably, after reinfection with L. monocytogenes, LLO91-99-specific T cells have a narrower TCR repertoire than do primary effector or memory T cells. Thus, our studies show that the TCR repertoire of primary effector T lymphocytes is uniformly transmitted to memory T cells, whereas expansion of memory T cells is selective.
T细胞记忆产生和维持的潜在机制仍不清楚。在本研究中,我们检测了单核细胞增生李斯特菌感染后,从初始效应T细胞向记忆T细胞转变过程中一个复杂的、抗原特异性T细胞群体的演变。使用四聚体H2-Kd-表位复合物在免疫脾中直接鉴定了针对李斯特菌溶素O(LLO)91-99的T细胞群体,LLO91-99是H2-Kd限制性T淋巴细胞识别的免疫显性表位。通过用一组单克隆抗体进行直接的体外染色来确定特异性T细胞的T细胞受体(TCR)Vβ谱。我们证明LLO91-99特异性的初始效应T细胞群体具有多样化的TCR Vβ谱。对记忆T细胞群体的分析显示出相似的TCR多样性。此外,对个体小鼠的实验表明,初始效应T细胞和记忆T细胞具有难以区分的TCR谱。值得注意的是,在用单核细胞增生李斯特菌再次感染后,LLO91-99特异性T细胞的TCR谱比初始效应T细胞或记忆T细胞的更窄。因此,我们的研究表明,初始效应T淋巴细胞的TCR谱被均匀地传递给记忆T细胞,而记忆T细胞的扩增是选择性的。