T Cells Localize with Proliferating Smooth Muscle α-Actin+ Cell Compartments in Asthma

Rationale Airway remodeling in asthma comprises increased airway smooth muscle (ASM), an alteration linked to airway hyperresponsiveness and disease severity. Experimental studies showed that T cells adhere to ASM through vascular cell adhesion molecule-1 (VCAM-1) and drive ASM growth through direct contact between the T cells and smooth muscle α-actin (α-SMA)+ cells. Objectives To support the hypothesis of a T-cell/α-SMA+ cell contact mechanism of ASM remodeling in asthma, using bronchial biopsies. Methods We performed quantitative morphology on T cells, proliferating cell nuclear antigen (PCNA), α-SMA, and VCAM-1 on biopsies from subjects with moderate and severe asthma and healthy control subjects. Measurements and Main Results We demonstrate ASM cell proliferation and infiltration by T cells in proportion to severity in the subjects with asthma. T cells localized with α-SMA+PCNA+ cells, suggesting direct intercellular contact and a relationship with α-SMA+ cell proliferation. Furthermore, the subjects with asthma developed a proliferating compartment of subepithelial α-SMA+, nonorganized airway contractile elements (NOACE), suggesting a phenotype gradient from undifferentiated cells to smooth muscle–like cells. T-cell juxtaposition events were also observed in this compartment and correlated to its mass. The subjects with asthma showed VCAM-1 expression in postcapillary venules and clusters of VCAM-1 immunoreactivity in ASM and NOACE, consistent with a role of VCAM-1 in T-cell/α-SMA+ cell interaction. Conclusions T cells may induce α-SMA+ cell proliferation through direct intercellular contact. NOACE may in part contribute to ASM growth through differentiation and translocation of α-SMA+ cells. The findings support the role of the T cell in ASM remodeling in asthma.