T-lymphocytes regulate genetically determined airway hyperresponsiveness in mice.
Airway hyperresponsiveness (AHR) is a hallmark of asthma and a heritable polygenic trait in the mouse. In the mouse, candidate gene products of hematopoietic origin implicated in asthma mapped to the regions of the previously defined quantitative trait loci. Since hematopoietic cells have been implicated in the pathogenesis of asthma, we evaluated the role of hematopoietic cells in general and T cells specifically in the genetic modulation of native airway responsiveness in mice. Here, with the use of bone marrow transplantation, anti-T-cell monoclonal antibody treatment and T-cell transfer, we demonstrate that intrinsic non-atopic AHR is mediated by T lymphocytes. Our data support the novel concept that, in the absence of identified environmental influences, T cells enhance genetically determined airway responsiveness.
De Sanctis
G T
GT
Combined Program in Pulmonary and Critical Care Medicine, Brigham & Women's Hospital, Boston, Massachusetts, USA.
Itoh
A
A
Green
F H
FH
Qin
S
S
Kimura
T
T
Grobholz
J K
JK
Martin
T R
TR
Maki
T
T
Drazen
J M
JM
D019264:Adoptive Transfer; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D016026:Bone Marrow Transplantation; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008212:Lymphocyte Depletion; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D012137:Respiratory System / Q000276:immunology*; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D013934:Thymectomy
D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride