T Cells localize with proliferating smooth muscle alpha-actin+ cell compartments in asthma.
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.
Ramos-Barbón
David
D
Meakins-Christie Laboratories, McGill University, Montreal, PQ, Canada.
Fraga-Iriso
Rebeca
R
Brienza
Nadia S
NS
Montero-Martínez
Carmen
C
Verea-Hernando
Héctor
H
Olivenstein
Ron
R
Lemiere
Catherine
C
Ernst
Pierre
P
Hamid
Qutayba A
QA
Martin
James G
JG
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
D000199:Actins; D018809:Proliferating Cell Nuclear Antigen; D019010:Vascular Cell Adhesion Molecule-1