Andersson Jan, Boasso Adriano, Nilsson Jakob, Zhang Rui, Shire Norah J, Lindback Stefan, Shearer Gene M, Chougnet Claire A
Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
J Immunol. 2005 Mar 15;174(6):3143-7. doi: 10.4049/jimmunol.174.6.3143.
Inadequate local cell-mediated immunity appears crucial for the establishment of chronic HIV infection. Accumulation of regulatory T cells (Treg) at the site of HIV replication, the lymphoid organs, may influence the outcome of HIV infection. Our data provide the first evidence that chronic HIV infection changes Treg tissue distribution. Several molecules characteristics of Treg (FoxP3, CTLA-4, glucocorticoid-induced TNFR family-related receptor, and CD25) were expressed more in tonsils of untreated patients compared with antiretroviral-treated patients. Importantly, most FoxP3+ cells expressed CTLA-4, but not CD69. Furthermore, a direct correlation between FoxP3 levels and viral load was evident. In contrast, FoxP3 expression was decreased in circulating T cells from untreated patients, but normalized after initiation of treatment. Functional markers of Treg activity (indoleamine 2,3-dioxygenase, TGF-beta, and CD80) were markedly increased in the tonsils of untreated patients. Our data could provide a new basis for immune-based therapies that counteract in vivo Treg and thereby reinforce appropriate antiviral immunity.
局部细胞介导的免疫功能不足似乎对慢性HIV感染的建立至关重要。调节性T细胞（Treg）在HIV复制部位即淋巴器官的积聚可能会影响HIV感染的结果。我们的数据首次证明慢性HIV感染会改变Treg的组织分布。与接受抗逆转录病毒治疗的患者相比，未经治疗患者扁桃体中几种Treg的分子特征（FoxP3、CTLA-4、糖皮质激素诱导的TNFR家族相关受体和CD25）表达更多。重要的是，大多数FoxP3+细胞表达CTLA-4，但不表达CD69。此外，FoxP3水平与病毒载量之间存在明显的直接相关性。相反，未经治疗患者循环T细胞中的FoxP3表达降低，但在开始治疗后恢复正常。未经治疗患者扁桃体中Treg活性的功能标志物（吲哚胺2,3-双加氧酶、TGF-β和CD80）明显增加。我们的数据可为基于免疫的疗法提供新的依据，这种疗法可在体内对抗Treg，从而增强适当的抗病毒免疫力。
