Bidirectional crosstalk between T lymphocytes and airway smooth muscle

T细胞与呼吸道平滑肌(ASM)细胞的接触触发其生长，ASM进而促进T细胞的存活和增殖。干预接触可促进T细胞的凋亡，也可干扰ASM的增殖。一种新的细胞间通讯方法是通过纳米管，即从T细胞到ASM的薄细胞突起。我们证明了抗凋亡因子如BCL2和MCL1存在于纳米管中，并且我们观察到线粒体从ASM转移到T细胞。我们已经证明了碱性成纤维细胞生长因子-2在纳米管形成中的作用(附录4)。然而，我们对通过纳米管在这些类型的细胞之间进行交流的生物学后果知之甚少。一般的假设是，CD4+T细胞通过影响ASM和T细胞生物学的纳米管与ASM细胞进行交流。为了了解T细胞和ASM细胞之间形成纳米管的生物学后果，形成纳米管的驱动因素以及这种细胞间通讯导致的细胞性质的变化，我们将进行以下一般领域的研究：

Contact of T cells with airway smooth muscle (ASM) cells triggers its growth and in turn ASM enhances T cell survival and proliferation. Interfering with contact augments T cell apoptosis and also interferes with ASM proliferation. A novel method of communication between the cells is through nanotubes, thin cellular projections from T cells to ASM. We demonstrated that anti-apoptotic factors such as Bcl2 and Mcl1 were present within the nanotubes and we have observed mitochondrial transfer from ASM to T cells. We have demonstrated a role for basic fibroblast growth factor-2 (bFGF-2) in nanotube formation (Appendix 4). However we know little of the biological consequences of communication via nanotubes between these cell types. The general hypothesis is that CD4+ T cells communicate with ASM cells via nanotubes that affect both ASM and T cell biology. To understand the biological consequences of nanotube formation between T cells and ASM cells, the drivers of the nanotube formation and the alterations in properties of the cells consequent upon this intercellular communication we will pursue the following general areas of research: