title: T Cells localize with proliferating smooth muscle alpha-actin+ cell compartments in asthma.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To support the hypothesis of a T-cell/alpha-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), alpha-SMA, and VCAM-1 on biopsies from subjects with moderate and severe asthma and healthy control subjects.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montreal, PQ, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Ramos-Barbón
authors.forename: Rebeca
authors.initials: R
authors.lastname: Fraga-Iriso
authors.forename: Nadia S
authors.initials: NS
authors.lastname: Brienza
authors.forename: Carmen
authors.initials: C
authors.lastname: Montero-Martínez
authors.forename: Héctor
authors.initials: H
authors.lastname: Verea-Hernando
authors.forename: Ron
authors.initials: R
authors.lastname: Olivenstein
authors.forename: Catherine
authors.initials: C
authors.lastname: Lemiere
authors.forename: Pierre
authors.initials: P
authors.lastname: Ernst
authors.forename: Qutayba A
authors.initials: QA
authors.lastname: Hamid
authors.forename: James G
authors.initials: JG
authors.lastname: Martin
mesh_terms: D000199:Actins / Q000378:metabolism*; D056151:Airway Remodeling; D001249:Asthma / Q000473:pathology*; D001706:Biopsy; D001980:Bronchi / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D006801:Humans; D009130:Muscle, Smooth / Q000166:cytology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000199:Actins; D018809:Proliferating Cell Nuclear Antigen; D019010:Vascular Cell Adhesion Molecule-1