Herron L R, Eisenberg R A, Roper E, Kakkanaiah V N, Cohen P L, Kotzin B L
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
J Immunol. 1993 Oct 1;151(7):3450-9.
The development of double-negative (CD4-, CD8-) T cells and other T cells subsets in lymphoproliferation (lpr) mice continues to be poorly defined. Recent studies indicate that lpr is a mutation of a receptor mediating apoptosis. It has thus been hypothesized that T cell development in the thymus should be abnormally affected. In this study, we analyzed the TCR V beta repertoire of double-negative T cells as well as CD4+ and CD8+ single-positive subsets in various lpr and matched non-lpr strains. Particular comparisons were made to determine the influence of different class I and class II molecules on repertoire formation. The data demonstrate that positive and negative selection of the CD4+ and CD8+ subsets are normal in lpr mice when compared with non-lpr congenic mice. Surprisingly, the result also suggest that double-negative T cells are mostly selected on class I MHC molecules in a pattern similar to the CD8+ population, and that T cells positively selected on class II MHC antigens may be absent from the double-negative population. In all lpr strains, we also found an increased percentage of double-negative V beta 8.3+ cells out of proportion to levels in the CD4+ or CD8+ subsets. Longitudinal studies and studies in thymectomized animals showed that this increase reflects a peripheral process selectively affecting V beta 8.3+ double-negative T cells. Together, these repertoire data provide new insight into the effect of the lpr genetic defect on T cell development and the derivation of double-negative T cells. Despite the role of Fas in apoptosis and the abnormal expression of this gene in lpr mice, the present results support the hypothesis that thymic events are relatively normal in lpr mice, and that the double-negative T cells are mostly class I MHC selected and expanded by abnormal peripheral processes.
淋巴增殖（lpr）小鼠中双阴性（CD4-、CD8-）T细胞及其他T细胞亚群的发育情况仍不清楚。最近的研究表明，lpr是一种介导细胞凋亡的受体发生的突变。因此有人推测，胸腺中的T细胞发育应该受到异常影响。在本研究中，我们分析了各种lpr及匹配的非lpr品系中双阴性T细胞以及CD4+和CD8+单阳性亚群的TCR Vβ谱。进行了特别比较以确定不同的I类和II类分子对谱形成的影响。数据表明，与非lpr同基因小鼠相比，lpr小鼠中CD4+和CD8+亚群的阳性和阴性选择是正常的。令人惊讶的是，结果还表明，双阴性T细胞大多在I类MHC分子上以与CD8+群体相似的模式被选择，并且双阴性群体中可能不存在在II类MHC抗原上被阳性选择的T细胞。在所有lpr品系中，我们还发现双阴性Vβ8.3+细胞的百分比增加，与CD4+或CD8+亚群中的水平不成比例。纵向研究和对胸腺切除动物的研究表明，这种增加反映了一个选择性影响Vβ8.3+双阴性T细胞的外周过程。总之，这些谱数据为lpr基因缺陷对T细胞发育及双阴性T细胞衍生的影响提供了新的见解。尽管Fas在细胞凋亡中起作用且该基因在lpr小鼠中表达异常，但目前的结果支持以下假设：lpr小鼠中的胸腺事件相对正常，并且双阴性T细胞大多由I类MHC选择并通过异常的外周过程扩增。
