Changes in thymic function with age and during the treatment of HIV infection
Changes in thymic function with age and during the treatment of HIV infection
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作者：
Douek, DC;McFarland, RD;Koup, RA
胸腺是表达 αβ 型 T 细胞抗原受体的 T 细胞产生和生成的主要部位(1)。与年龄相关的退化(2)可能会影响胸腺重建表达CD4细胞表面抗原的T细胞的能力，这些抗原在HIV感染期间丢失(3)；这种效果在化疗和骨髓移植后已经可见(4,5)。接受高效抗逆转录病毒疗法 (HAART) 治疗的成年 HIV 感染患者的初始 CD4 阳性 T 细胞数量逐渐增加 (6,7)。这些细胞可能是通过外周现有初始 T 细胞的扩增 (8) 或通过胸腺产生新的初始 T 细胞 (9,10) 产生的。在这里，我们通过测量 TCR 基因重排的切除 DNA 产物来量化胸腺输出。我们发现，尽管胸腺功能随着年龄的增长而下降，但大量的产出一直保持到成年后期。 HIV 感染会导致胸腺功能下降，可在外周血和淋巴组织中检测到。在接受HAART治疗的成人中，大多数受试者的胸腺输出量出现快速且持续的增加。这些结果表明，成年胸腺扇有助于 HAART 后的免疫重建。
The thymus represents the major site of the production and generation of T cells expressing alpha beta-type T-cell antigen receptors(1). Age-related involution(2) may affect the ability of the thymus to reconstitute T cells expressing CD4 cell-surface antigens that are lost during HIV infection(3); this effect has been seen after chemotherapy and bone-marrow transplantation(4,5). Adult HIV-infected patients treated with highly active antiretroviral therapy (HAART) show a progressive increase in their number of naive CD4-positive T cells(6,7). These cells could arise through expansion of existing naive T cells in the periphery(8) or through thymic production of new naive T cells(9,10). Here we quantify thymic output by measuring the excisional DNA products of TCR-gene rearrangement. We find that, although thymic function declines with age, substantial output is maintained into late adulthood. HIV infection leads to a decrease in thymic function that can be measured in the peripheral blood and lymphoid tissues. In adults treated with HAART, there is a rapid and sustained increase in thymic output in most subjects. These results indicate that the adult thymus fan contribute to immune reconstitution following HAART.