Bidirectional crosstalk between T lymphocytes and airway smooth muscle

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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: