Douek D C, McFarland R D, Keiser P H, Gage E A, Massey J M, Haynes B F, Polis M A, Haase A T, Feinberg M B, Sullivan J L, Jamieson B D, Zack J A, Picker L J, Koup R A
Department of Medicine, The University of Texas Southwestern Medical Center, Dallas 75235, USA.
Nature. 1998 Dec 17;396(6712):690-5. doi: 10.1038/25374.
The thymus represents the major site of the production and generation of T cells expressing alphabeta-type T-cell antigen receptors. Age-related involution may affect the ability of the thymus to reconstitute T cells expressing CD4 cell-surface antigens that are lost during HIV infection; this effect has been seen after chemotherapy and bone-marrow transplantation. Adult HIV-infected patients treated with highly active antiretroviral therapy (HAART) show a progressive increase in their number of naive CD4-positive T cells. These cells could arise through expansion of existing naive T cells in the periphery or through thymic production of new naive T cells. 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 can contribute to immune reconstitution following HAART.
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场所。与年龄相关的退化可能会影响胸腺重建在HIV感染期间丢失的表达CD4细胞表面抗原的T细胞的能力；这种效应在化疗和骨髓移植后已被观察到。接受高效抗逆转录病毒疗法（HAART）治疗的成年HIV感染患者，其幼稚CD4阳性T细胞数量逐渐增加。这些细胞可能通过外周现有幼稚T细胞的扩增或通过胸腺产生新的幼稚T细胞而产生。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，尽管胸腺功能随年龄下降，但在成年后期仍维持大量输出。HIV感染导致胸腺功能下降，这可以在外周血和淋巴组织中检测到。在接受HAART治疗的成年人中，大多数受试者的胸腺输出迅速且持续增加。这些结果表明，成年胸腺可有助于HAART后的免疫重建。
