Structural and Functional Consequences of Alveolar Cell Recognition by CD8 (+) T Lymphocytes in Experimental Lung Disease

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Abstract

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. (J. Clin. Invest. 1998. 102:1653-1661.)

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