title: Severe Reduction in Number and Function of Peripheral T Cells Does Not Afford Protection toward Emphysema and Bronchial Remodeling Induced in Mice by Cigarette Smoke.
abstract: The protein Lck (p56(Lck)) is a Src family tyrosine kinase expressed at all stages of thymocyte development and is required for maturation of T cells. The targeted disruption of Lck gene in mice results in severe block in thymocyte maturation with substantial reduction in the development of CD4(+)CD8(+) thymocytes, severe reduction of peripheral T cells, and disruption of T-cell receptor signaling with defective function of T-cell responses. To investigate the role of T lymphocyte in the development of cigarette smoke-induced pulmonary changes, Lck(-/-) mice and corresponding congenic wild-type mice were chronically exposed to cigarette smoke, and their lungs were analyzed by biochemical, immunologic, and morphometric methods. Smoking mice from both genotypes showed disseminated foci of emphysema and large areas of goblet cell metaplasia in bronchial and bronchiolar epithelium. Morphometric evaluation of lung changes and lung elastin determination confirmed that mice from both genotypes showed the same degree of emphysematous lesions. Thus, cigarette smoke exposure in the presence of severe reduction in number and function of peripheral T cells does not influence the development of pulmonary changes induced by cigarette smoke. The data obtained suggest that innate immunity is a leading actor in the early development of pulmonary changes in smoking mice and that the adaptive immune response may play a role at later stages.
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: De Cunto
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Lunghi
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bartalesi
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Cavarra
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fineschi
authors.affiliation: Department of Life Sciences, University of Siena, Siena, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ulivieri
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. Electronic address: giuseppe.lungarella@unisi.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lungarella
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. Electronic address: monica.lucattelli@unisi.it.
authors.forename: Monica
authors.initials: M
authors.lastname: Lucattelli
mesh_terms: D000818:Animals; D001980:Bronchi / Q000473:pathology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007150:Immunohistochemistry; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000172:deficiency; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011656:Pulmonary Emphysema / Q000276:immunology* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)