The role of CD44 in bidirectional crosstalk between smooth muscle and T lymphocytes

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Studies have shown that activated T cells can adhere to airway smooth muscle (ASM) cells via CD44 and integrins and induce proliferation of ASM cells. Our preliminary data indicate an important role for the epidermal growth factor receptor (EGFR) in driving this proliferation. There are several EGFR ligands, epidermal growth factor (EGF), heparin-binding epidermal growth factor (HB-EGF), amphiregulin (Areg), ß-cellulin, transforming growth factor-a (TGF- a) and epiregulin. CD4+ Th2 cells have been shown to express Areg. The EGFR ligands are present in the cell membrane in pro-forms that are released by sheddases such as the matrix metalloproteinases (MMPs). Several ligands are upregulated in CD4+ T cells in co-culture with ASM cells and the T cells are protected from apoptosis.