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

• Published in: American journal of respiratory and critical care medicine 2010-08, Vol.182 (3), p.317-324
• Main Authors: RAMOS-BARBON, David, FRAGA-IRISO, Rebeca, BRIENZA, Nadia S, MONTERO-MARTINEZ, Carmen, VEREA-HERNANDO, Héctor, OLIVENSTEIN, Ron, LEMIERE, Catherine, ERNST, Pierre, HAMID, Qutayba A, MARTIN, James G
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Airway Remodeling; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Asthma - pathology; Biological and medical sciences; Biopsy; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Bronchi - pathology; Case-Control Studies; Cell Proliferation; Humans; Intensive care medicine; Medical sciences; Muscle, Smooth - cytology; Proliferating Cell Nuclear Antigen - metabolism; Severity of Illness Index; T-Lymphocytes - physiology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200905-0745OC

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 alpha-actin (alpha-SMA)(+) cells. To support the hypothesis of a T-cell/alpha-SMA(+) cell contact mechanism of ASM remodeling in asthma, using bronchial biopsies. We performed quantitative morphology on T cells, proliferating cell nuclear antigen (PCNA), alpha-SMA, and VCAM-1 on biopsies from subjects with moderate and severe asthma and healthy control subjects. We demonstrate ASM cell proliferation and infiltration by T cells in proportion to severity in the subjects with asthma. T cells localized with alpha-SMA(+)PCNA(+) cells, suggesting direct intercellular contact and a relationship with alpha-SMA(+) cell proliferation. Furthermore, the subjects with asthma developed a proliferating compartment of subepithelial alpha-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/alpha-SMA(+) cell interaction. T cells may induce alpha-SMA(+) cell proliferation through direct intercellular contact. NOACE may in part contribute to ASM growth through differentiation and translocation of alpha-SMA(+) cells. The findings support the role of the T cell in ASM remodeling in asthma.