Gabor M J, Scollay R, Godfrey D I
Centenary Institute of Cancer Medicine and Cell Biology, Sydney, Australia.
Eur J Immunol. 1997 Nov;27(11):2986-93. doi: 10.1002/eji.1830271135.
The peripheral T cell pool is maintained both by export of naive T cells from the thymus and by post-thymic expansion of activated/memory T cells. However, it is not known whether the thymus can alter its output following peripheral T cell depletion. Using intrathymic injection of fluorescein isothiocyanate to detect recent thymic emigrants (RTE), we directly tested whether the thymus is able to alter the number of RTE or the CD4:CD8 ratio of RTE emigrating to the periphery in response to in vivo depletion of total peripheral T cells or CD4 T cells, respectively. Depletion of peripheral T cells was achieved with anti-Thy-1 or anti-CD4, at doses that did not affect thymocyte numbers. Depletion of greater than 70% of peripheral T cells by treatment with anti-Thy-1 in vivo did not alter the number or cell cycle status of RTE trafficking to lymph nodes or spleen during the peripheral reconstitution phase (6, 9, 12 days). Similarly, depletion of the majority of CD4 T cells, which significantly reduced the peripheral CD4:CD8 T cell ratio, did not alter the total number or the proportion of CD4+ CD8- RTE in peripheral lymphoid organs. These data clearly indicate that thymic output is not influenced by downstream alterations in peripheral T cell pool size or CD4:CD8 ratio. Rather we contend that thymic T cell export is internally regulated by as yet undefined mechanisms.
外周T细胞库通过胸腺中幼稚T细胞的输出以及活化/记忆T细胞在胸腺后的扩增来维持。然而,尚不清楚胸腺是否能在周围T细胞耗竭后改变其输出。通过胸腺内注射异硫氰酸荧光素来检测近期胸腺迁出细胞(RTE),我们分别直接测试了胸腺是否能够响应体内总外周T细胞或CD4 T细胞的耗竭,改变迁出至外周的RTE数量或RTE的CD4:CD8比例。外周T细胞的耗竭通过抗Thy-1或抗CD4实现,剂量不影响胸腺细胞数量。在体内用抗Thy-1治疗使外周T细胞耗竭超过70%,在周围重建阶段(6、9、12天)并未改变迁移至淋巴结或脾脏的RTE数量或细胞周期状态。同样,耗竭大多数CD4 T细胞(这显著降低了外周CD4:CD8 T细胞比例)并未改变外周淋巴器官中CD4+CD8-RTE的总数或比例。这些数据清楚地表明,胸腺输出不受外周T细胞库大小或CD4:CD8比例的下游改变影响。相反,我们认为胸腺T细胞输出受尚未明确的机制内在调节。