Berzins S P, Boyd R L, Miller J F
Department of Pathology and Immunology, Monash Medical School, Prahran 3181, Victoria, Australia.
J Exp Med. 1998 Jun 1;187(11):1839-48. doi: 10.1084/jem.187.11.1839.
The thymus is essential for the initial seeding of T cells to the periphery, but its role in maintaining the adult T cell pool remains poorly defined. We investigated whether changes to the rate of T cell export could form part of the mechanism(s) controlling the homeostatic regulation of the size and composition of the peripheral T cell pool. Using neonatal thymi grafted under the kidney capsule, we found that irrespective of whether the pool was oversupplied (by thymic grafts) or undersupplied (due to neonatal thymectomy), the thymic export rate was constant from both the host and graft thymus, and the periphery remained constant in size. Recent thymic emigrants (RTE) were also tracked to determine the extent of their acceptance into the T cell pool of a normal mouse. As a population, RTE are phenotypically mature, but were distinct from resident T cells in the periphery, being released in a CD4/CD8 ratio approximately twice that of established peripheral T cells. This export ratio is similar to that of T cells in the mature thymic compartment, but soon after entry into the periphery, the ratio falls, indicating separate thymic and peripheral regulation of the CD4/CD8 ratio. RTE may also be preferentially incorporated into the periphery, causing displacement of resident T cells, thus maintaining the size of the peripheral pool. Although not vital for the maintenance of a functional T cell pool, the acceptance of RTE in a "full" peripheral pool would ensure that the T cell receptor repertoire is kept diverse and that the T cell population encompasses a broad range of naive as well as memory T cells.
胸腺对于T细胞初次向外周播散至关重要,但其在维持成年T细胞库方面的作用仍不明确。我们研究了T细胞输出速率的变化是否可能构成控制外周T细胞库大小和组成的稳态调节机制的一部分。通过将新生胸腺移植到肾被膜下,我们发现,无论T细胞库是供应过多(由于胸腺移植)还是供应不足(由于新生期胸腺切除),宿主和移植胸腺的胸腺输出速率都是恒定的,外周T细胞库的大小也保持不变。我们还追踪了近期胸腺迁出细胞(RTE),以确定它们被正常小鼠T细胞库接纳的程度。作为一个群体,RTE在表型上是成熟的,但与外周的驻留T细胞不同,它们以大约是成熟外周T细胞两倍的CD4/CD8比例释放。这种输出比例与成熟胸腺区室中的T细胞比例相似,但进入外周后不久,该比例就会下降,这表明胸腺和外周对CD4/CD8比例存在独立调节。RTE也可能优先整合到外周,导致驻留T细胞被取代,从而维持外周T细胞库的大小。虽然对于维持功能性T细胞库并非至关重要,但RTE被“完整”外周T细胞库接纳将确保T细胞受体库保持多样化,并且T细胞群体包含广泛的初始T细胞以及记忆T细胞。