Mackall C L, Punt J A, Morgan P, Farr A G, Gress R E
Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD, USA.
Eur J Immunol. 1998 Jun;28(6):1886-93. doi: 10.1002/(SICI)1521-4141(199806)28:06<1886::AID-IMMU1886>3.0.CO;2-M.
Age-associated thymic involution results in a diminished capacity to regenerate T cell populations, although the magnitude of this effect is unknown. In this report, thymic function was studied in aged vs. young adult mice after lethal irradiation and administration of T cell-depleted bone marrow (BM) from young mice. Abnormalities observed in aged thymi (reduced thymocyte numbers, histologic abnormalities) were not reversed by administration of young BM via bone marrow transplantation (BMT), but aged thymi displayed a normal thymocyte subset distribution and appropriately deleted MIs-reactive T cells after BMT. Aged BMT recipients regenerated significantly reduced numbers of splenic T cells compared to young recipients and showed increased peripheral expansion of thymic emigrants since a higher proportion of BM-derived T cells expressed a memory phenotype in aged vs. young BMT recipients. Because peripheral expansion of thymic emigrants could substantially increase the number of thymic progeny present in the spleen, we sought to measure thymic T cell regenerative capacity after BMT in a setting devoid of peripheral expansion. To do this, TCR-transgenic (Tg+) T cell-depleted BM was administered to aged and young recipients lacking antigen specific for the Tg+ TCR. Aged recipients regenerated approximately 50 % of the TCR Tg+ cells regenerated in young BMT recipients, providing evidence that even very aged thymi retain the capacity to regenerate significant numbers of mature T cell progeny. Therefore, thymic function is reduced with aged but it is not lost, suggesting that therapeutic approaches to enhance thymic function may be successful even in very aged hosts.
与年龄相关的胸腺退化导致T细胞群体再生能力下降，尽管这种影响的程度尚不清楚。在本报告中，研究了老年小鼠与年轻成年小鼠在接受致死性照射并给予来自年轻小鼠的T细胞耗竭骨髓（BM）后的胸腺功能。通过骨髓移植（BMT）给予年轻BM并不能逆转老年胸腺中观察到的异常（胸腺细胞数量减少、组织学异常），但老年胸腺在BMT后显示出正常的胸腺细胞亚群分布，并能适当清除自身免疫反应性T细胞。与年轻受体相比，老年BMT受体脾脏T细胞的再生数量显著减少，并且胸腺迁出细胞的外周扩增增加，因为与年轻BMT受体相比，老年受体中更高比例的BM来源T细胞表达记忆表型。由于胸腺迁出细胞的外周扩增可大幅增加脾脏中胸腺后代的数量，我们试图在没有外周扩增的情况下测量BMT后胸腺T细胞的再生能力。为此，将TCR转基因（Tg+）T细胞耗竭的BM给予缺乏针对Tg+ TCR的抗原特异性的老年和年轻受体。老年受体再生的TCR Tg+细胞约为年轻BMT受体再生数量的50%，这表明即使是非常年老的胸腺仍保留再生大量成熟T细胞后代的能力。因此，胸腺功能随年龄增长而降低，但并未丧失，这表明增强胸腺功能的治疗方法即使在非常年老的宿主中也可能成功。
