Hu Haitao, Fernando Kathy, Ni Houping, Weissman Drew
Division of Infectious Diseases, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
J Immunol. 2008 Apr 15;180(8):5593-600. doi: 10.4049/jimmunol.180.8.5593.
We previously demonstrated that HIV envelope glycoprotein (Env), delivered in the form of a vaccine and expressed by dendritic cells or 293T cells, could suppress Ag-stimulated CD4(+) T cell proliferation. The mechanism remains to be identified but is dependent on CD4 and independent of coreceptor binding. Recently, CD4(+) regulatory T (Treg) cells were found to inhibit protective anti-HIV CD4(+) and CD8(+) T cell responses. However, the role of Tregs in HIV remains highly controversial. HIV Env is a potent immune inhibitory molecule that interacts with host CD4(+) cells, including Treg cells. Using an in vitro model, we investigated whether Treg cells are involved in Env-induced suppression of CD4(+) T cell proliferation, and whether Env directly affects the functional activity of Treg cells. Our data shows that exposure of human CD4(+) T cells to Env neither induced a higher frequency nor a more activated phenotype of Treg cells. Depletion of CD25(+) Treg cells from PBMC did not overcome the Env-induced suppression of CD4(+) T cell proliferation, demonstrating that CD25(+)FoxP3(+) Treg cells are not involved in Env-induced suppression of CD4(+) T cell proliferation. In addition, we extend our observation that similar to Env expressed on cells, Env present on virions also suppresses CD4(+) T cell proliferation.
我们之前证明，以疫苗形式递送并由树突状细胞或293T细胞表达的HIV包膜糖蛋白（Env）可抑制抗原刺激的CD4(+) T细胞增殖。其机制尚待确定，但依赖于CD4且不依赖于共受体结合。最近，发现CD4(+)调节性T（Treg）细胞可抑制保护性抗HIV CD4(+)和CD8(+) T细胞反应。然而，Tregs在HIV中的作用仍极具争议。HIV Env是一种与包括Treg细胞在内的宿主CD4(+)细胞相互作用的强效免疫抑制分子。利用体外模型，我们研究了Treg细胞是否参与Env诱导的CD4(+) T细胞增殖抑制，以及Env是否直接影响Treg细胞的功能活性。我们的数据表明，人CD4(+) T细胞暴露于Env既未诱导Treg细胞出现更高频率，也未诱导其出现更活化的表型。从外周血单核细胞中去除CD25(+) Treg细胞并不能克服Env诱导的CD4(+) T细胞增殖抑制，这表明CD25(+)FoxP3(+) Treg细胞不参与Env诱导的CD4(+) T细胞增殖抑制。此外，我们进一步观察到，与细胞上表达的Env类似，病毒颗粒上的Env也能抑制CD4(+) T细胞增殖。
