Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
PLoS One. 2011;6(12):e28629. doi: 10.1371/journal.pone.0028629. Epub 2011 Dec 14.
Interleukin-7 (IL-7) concentrations are increased in the blood of CD4+ T cell depleted individuals, including HIV-1 infected patients. High IL-7 levels might stimulate T cell activation and, as we have shown earlier, IL-7 can prime resting T cell to CD95 induced apoptosis as well. HIV-1 infection leads to B cell abnormalities including increased apoptosis via the CD95 (Fas) death receptor pathway and loss of memory B cells. Peripheral B cells are not sensitive for IL-7, due to the lack of IL-7Ra expression on their surface; however, here we demonstrate that high IL-7 concentration can prime resting B cells to CD95-mediated apoptosis via an indirect mechanism. T cells cultured with IL-7 induced high CD95 expression on resting B cells together with an increased sensitivity to CD95 mediated apoptosis. As the mediator molecule responsible for B cell priming to CD95 mediated apoptosis we identified the cytokine IFN-γ that T cells secreted in high amounts in response to IL-7. These results suggest that the lymphopenia induced cytokine IL-7 can contribute to the increased B cell apoptosis observed in HIV-1 infected individuals.
白细胞介素-7（IL-7）浓度在 CD4+T 细胞耗竭个体的血液中升高，包括 HIV-1 感染患者。高 IL-7 水平可能会刺激 T 细胞活化，正如我们之前所表明的，IL-7 还可以将静止的 T 细胞引发为 CD95 诱导的细胞凋亡。HIV-1 感染导致 B 细胞异常，包括通过 CD95（Fas）死亡受体途径增加凋亡和记忆 B 细胞丧失。外周 B 细胞对 IL-7 不敏感，因为它们表面缺乏 IL-7Ra 表达；然而，在这里我们证明高浓度的 IL-7 可以通过间接机制将静止的 B 细胞引发为 CD95 介导的凋亡。与增加的对 CD95 介导的凋亡的敏感性一起，用 IL-7 培养的 T 细胞诱导静止 B 细胞上的高 CD95 表达。作为负责将 B 细胞引发为 CD95 介导的凋亡的中介分子，我们确定了 T 细胞响应 IL-7 大量分泌的细胞因子 IFN-γ。这些结果表明，淋巴细胞减少诱导的细胞因子 IL-7 可能有助于 HIV-1 感染个体中观察到的 B 细胞凋亡增加。
