Structural and functional consequences of alveolar cell recognition by CD8(+) T lymphocytes in experimental lung disease.
CD8(+) T cells infiltrate the lung in many clinical conditions, particularly in interstitial lung disease. The role(s) that CD8(+) T cells might be playing in the pathogenesis of inflammatory lung disease is unclear at present, as is the direct contribution of CD8(+) T cell effector activities to lung injury. This report describes a transgenic model used to evaluate the impact, on respiratory structure and function, of CD8(+) T lymphocyte recognition of a target antigen expressed endogenously in alveolar epithelial cells. We found that adoptive transfer of cloned CD8(+) cytotoxic T lymphocytes (CTLs) specific for an alveolar neo-antigen (influenza hemagglutinin) leads to progressive lethal injury in transgenic mice, which dramatically affects lung structure and function. Transgenic recipients of CD8(+) CTLs exhibited tachypnea and progressive weight loss, becoming moribund over a period of several days. Concomitantly, the animals developed a progressive interstitial pneumonitis characterized initially by lymphocytic infiltration of alveolar walls and spaces, followed by an exuberant mononuclear cell infiltration that correlated with restrictive pulmonary mechanics and a progressive diffusion impairment. These results indicate that antigen-specific CD8(+) T cell recognition of an alveolar epithelial "autoantigen" is, in and of itself, sufficient to trigger an inflammatory cascade that results in the histological and physiological manifestations of interstitial pneumonia.
Enelow
R I
RI
The, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA. enelow@virginia.edu
Mohammed
A Z
AZ
Stoler
M H
MH
Liu
A N
AN
Young
J S
JS
Lou
Y H
YH
Braciale
T J
TJ
D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D002460:Cell Line; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008171:Lung Diseases / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D001324:Autoantigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus