Ye Ping, Kirschner Denise E, Kourtis Athena P
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Curr HIV Res. 2004 Apr;2(2):177-83. doi: 10.2174/1570162043484898.
The thymus is the primary lymphoid organ supplying new lymphocytes to the periphery. Clinical and morphologic studies of HIV-infected children and adults indicate that the thymus is affected by HIV. Thymic dysfunction and thymic involution occur during HIV disease and have been associated with rapid progression in infants infected perinatally with HIV. In vitro information of thymic organ culture, thymic epithelial cell culture, the SCID-hu mouse system and SHIV infection of primates have supported HIV-induced thymic damage. The mechanisms underlying this could be many, including direct thymocyte killing by the virus, apoptosis, or disruption of thymic stromal architecture. T cell receptor excision circles (TREC) have been developed as a marker of new thymic emigrants. Decreases in TREC concentrations have been found in both HIV-infected pediatric and adult patients. Mathematical models have suggested that thymic infection in children is more severe than in adults, particularly during infection with strains that use CXCR4 as coreceptor. Recent evidence suggests that thymic recovery may be achieved in some patients as a result of potent antiretroviral therapy. Extensive thymic damage may, however, hamper immune reconstitution, particularly in pediatric patients. This review attempts to summarize evidence for thymic involvement during HIV infection in children and in adults, the role of thymic infection in disease progression, and the contribution of the thymus to immune restoration following potent antiviral therapy. Immunologic interventions aiming at restoring thymic function in AIDS patients are also reviewed.
胸腺是向外周供应新淋巴细胞的主要淋巴器官。对感染HIV的儿童和成人的临床及形态学研究表明，胸腺会受到HIV的影响。在HIV疾病期间会出现胸腺功能障碍和胸腺退化，并且这与围产期感染HIV的婴儿病情快速进展有关。胸腺器官培养、胸腺上皮细胞培养、重症联合免疫缺陷人鼠系统以及灵长类动物的猴免疫缺陷病毒感染的体外研究信息都支持HIV对胸腺造成损害。其潜在机制可能有很多，包括病毒直接杀伤胸腺细胞、细胞凋亡或胸腺基质结构破坏。T细胞受体切除环（TREC）已被开发为新胸腺迁出细胞的标志物。在感染HIV的儿童和成人患者中均发现TREC浓度降低。数学模型表明，儿童的胸腺感染比成人更严重，尤其是在感染以CXCR4作为共受体的毒株时。最近的证据表明，由于有效的抗逆转录病毒疗法，一些患者的胸腺可能会恢复。然而，广泛的胸腺损伤可能会阻碍免疫重建，尤其是在儿科患者中。这篇综述试图总结儿童和成人HIV感染期间胸腺受累的证据、胸腺感染在疾病进展中的作用以及强效抗病毒治疗后胸腺对免疫恢复的贡献。还综述了旨在恢复艾滋病患者胸腺功能的免疫干预措施。
