Al Heialy Saba, Zeroual Melissa, Farahnak Soroor, McGovern Toby, Risse Paul-André, Novali Mauro, Lauzon Anne-Marie, Roman Horia N, Martin James G
Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec H2X 2P2, Canada; andResearch Institute, McGill University Health Centre, Montreal, Quebec H2X 2P2, Canada.
Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Quebec H2X 2P2, Canada; andResearch Institute, McGill University Health Centre, Montreal, Quebec H2X 2P2, Canada
J Immunol. 2015 Jun 15;194(12):5626-34. doi: 10.4049/jimmunol.1401718. Epub 2015 May 1.
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.
气道平滑肌（ASM）细胞与活化的CD4(+) 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细胞增殖并提高T细胞存活率。我们推测ASM与CD4(+) T细胞之间的直接接触通过纳米管促进了抗凋亡蛋白的转移，从而导致活化的CD4(+) T细胞存活率增加。从健康受试者外周血单核细胞（PBMC）中分离出的CD4(+) T细胞，在活化并与ASM细胞共培养24小时后，形成了纳米管，通过免疫荧光和原子力显微镜观察到。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。两种主要的抗凋亡蛋白，免疫反应性B细胞淋巴瘤2（Bcl-2）和诱导髓系白血病细胞分化蛋白（Mcl-1），存在于纳米管内。ASM细胞中通过小干扰RNA下调Mcl-1可显著增加T细胞凋亡，而下调Bcl-2则无影响。通过纳米管将绿色荧光蛋白标记的Mcl-1从ASM细胞转移到CD4(+) 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细胞通讯。Mcl-1通过纳米管从ASM直接转移到CD(+) T细胞参与了T细胞存活。本研究提供了一种依赖于与结构细胞相互作用的CD4(+) T细胞存活的新机制。
