Nanotubes Connect CD4+ T Cells to Airway Smooth Muscle Cells: Novel Mechanism of T Cell Survival
Nanotubes Connect CD4+ T Cells to Airway Smooth Muscle Cells: Novel Mechanism of T Cell Survival
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DOI：
10.4049/jimmunol.1401718
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发表时间：
2015-06-15
影响因子：
4.4
通讯作者：
Martin, James G.
中科院分区：
文献类型：
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作者：
Al Heialy, Saba;Zeroual, Melissa;Martin, James G.
气道平滑肌（ASM）细胞和活化的CD 4（+）T细胞之间的接触是哮喘等疾病中的关键相互作用，可触发ASM细胞增殖并增强T细胞存活。我们假设ASM和CD 4（+）T细胞之间的直接接触促进了抗凋亡蛋白通过纳米管的转移，导致活化的CD 4（+）T细胞的存活增加。从健康受试者的PBMC中分离的CD 4（+）T细胞，当活化并与ASM细胞共培养24小时时，形成通过免疫荧光和原子力显微镜观察到的纳米管。荧光染料钙黄绿素-AM的细胞间转移证实了通过纳米管的细胞质通讯。免疫反应性B细胞淋巴瘤2（Bcl-2）和诱导髓性白血病细胞分化蛋白（Mcl-1），两个主要的抗凋亡蛋白，存在于纳米管。在ASM细胞中通过小干扰RNA下调Mcl-1显著增加T细胞凋亡，而下调Bcl-2则没有影响。通过纳米管将GFP标记的Mcl-1从ASM细胞转移到CD 4（+）T细胞证实了转移的方向性。总之，活化的T细胞通过纳米管形成与ASM细胞通信。Mcl-1通过纳米管从ASM直接转移到CD+ T细胞参与T细胞存活。这项研究提供了一种依赖于与结构细胞相互作用的CD 4（+）T细胞存活的新机制。
Contact between airway smooth muscle (ASM) cells and activated CD4(+) T cells, a key interaction in diseases such as asthma, triggers ASM cell proliferation and enhances T cell survival. We hypothesized that direct contact between ASM and CD4(+) T cells facilitated the transfer of anti-apoptotic proteins via nanotubes, resulting in increased survival of activated CD4(+) T cells. CD4(+) T cells, isolated from PBMCs of healthy subjects, when activated and cocultured with ASM cells for 24 h, formed nanotubes that were visualized by immunofluorescence and atomic force microscopy. Cell-to-cell transfer of the fluorescent dye calcein-AM confirmed cytoplasmic communication via nanotubes. Immunoreactive B cell lymphoma 2 (Bcl-2) and induced myeloid leukemia cell differentiation protein (Mcl-1), two major anti-apoptotic proteins, were present within the nanotubes. Downregulation of Mcl-1 by small interfering RNA in ASM cells significantly increased T cell apoptosis, whereas downregulation of Bcl-2 had no effect. Transfer of GFP-tagged Mcl-1 from ASM cells to CD4(+) T cells via the nanotubes confirmed directionality of transfer. In conclusion, activated T cells communicate with ASM cells via nanotube formation. Direct transfer of Mcl-1 from ASM to CD+ T cells via nanotubes is involved in T cell survival. This study provides a novel mechanism of survival of CD4(+) T cells that is dependent on interaction with a structural cell.