Aguila H L, Hershberger R J, Weissman I L
Department of Pathology, Stanford University Medical Center, CA 94305, USA.
Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10192-6. doi: 10.1073/pnas.92.22.10192.
We have generated transgenic mice bearing the diphtheria toxin A chain (DTA) gene under the control of granzyme A (GrA) promoter sequences (GrA-DTA). GrA is expressed in activated cytotoxic cells but not in their immediate progenitors. These GrA-DTA mice are deficient in cytotoxic functions, indicating that most cytotoxic cells express GrA in vivo. Surprisingly, one founder strain containing a multicopy GrA-DTA insert show a marked and selective deficiency in CD8+ cells in peripheral lymphoid organs. This depletion was not observed in thymus, where the distribution of CD4+ and CD8+ cells is normal. Moreover, the emigration of T cells from thymus is normal, indicating that the depletion occurs in the periphery. GrA-DTA mice should be useful as models to dissect the role of cytotoxic cells in immune responses and as recipients of normal and neoplastic hematopoietic cells. The selective depletion of CD8+ cells in one founder strain could have implications for postthymic T-cell development.
我们构建了在颗粒酶A（GrA）启动子序列控制下携带白喉毒素A链（DTA）基因的转基因小鼠（GrA-DTA）。GrA在活化的细胞毒性细胞中表达，但在其直接祖细胞中不表达。这些GrA-DTA小鼠的细胞毒性功能缺陷，表明大多数细胞毒性细胞在体内表达GrA。令人惊讶的是，一个含有多拷贝GrA-DTA插入片段的奠基者品系在外周淋巴器官的CD8+细胞中表现出明显的选择性缺陷。在胸腺中未观察到这种耗竭，胸腺中CD4+和CD8+细胞的分布是正常的。此外，T细胞从胸腺的迁出是正常的，表明耗竭发生在外周。GrA-DTA小鼠作为剖析细胞毒性细胞在免疫反应中的作用的模型以及作为正常和肿瘤造血细胞的受体应该是有用的。一个奠基者品系中CD8+细胞的选择性耗竭可能对胸腺后T细胞发育有影响。
