CD8+ T Cells are required for inflammation and destruction in cigarette smoke-induced emphysema in mice.
Increased numbers of T lymphocytes are observed in the lungs of patients with chronic obstructive pulmonary disease, but their role in the disease process is not known. We investigated the role of CD8+ T cells in inflammatory cell recruitment and lung destruction in a cigarette smoke-induced murine model of emphysema. In contrast to wild-type C57BL/6J mice that displayed macrophage, lymphocyte, and neutrophil recruitment to the lung followed by emphysema in response to cigarette smoke, CD8+ T cell-deficient (CD8-/-) mice had a blunted inflammatory response and did not develop emphysema when exposed to long-term cigarette smoke. Further studies supported a pathogenetic pathway whereby the CD8+ T cell product, IFN-gamma-inducible protein-10, induces production of macrophage elastase (matrix metalloproteinase 12) that degrades elastin, both causing lung destruction directly and generating elastin fragments that serve as monocyte chemokines augmenting macrophage-mediated lung destruction. These studies demonstrate a requirement for CD8+ T cells for the development of cigarette smoke-induced emphysema and they provide a unifying pathway whereby CD8+ T cells are a central regulator of the inflammatory network in chronic obstructive pulmonary disease.
Maeno
Toshitaka
T
Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Houghton
A McGarry
AM
Quintero
Pablo A
PA
Grumelli
Sandra
S
Owen
Caroline A
CA
Shapiro
Steven D
SD
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D004549:Elastin / Q000378:metabolism; D008168:Lung / Q000276:immunology*; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009000:Monocytes / Q000276:immunology; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D012906:Smoke; D014026:Nicotiana / Q000633:toxicity
D012906:Smoke; D004549:Elastin; D053508:Matrix Metalloproteinase 12