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Am J Physiol Lung Cell Mol Physiol 276: L256-L262, 1999;
1040-0605/99 $5.00
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Vol. 276, Issue 2, L256-L262, February 1999

Production of interferon-gamma by lung lymphocytes in HIV-infected individuals

Homer L. Twigg III, Blake A. Spain, Diaa M. Soliman, Kenneth Knox, Richard A. Sidner, Carol Schnizlein-Bick, David S. Wilkes, and Gary K. Iwamoto

Divisions of Pulmonary/Critical Care Medicine and Infectious Diseases, Department of Medicine, and Department of Surgery, Indiana University Medical Center, Indianapolis, Indiana 46202

A CD8+ lymphocytic alveolitis occurs in up to 60% of asymptomatic human immunodeficiency virus (HIV)-infected individuals. Early in HIV infection, lymphocytes consist predominantly of cytotoxic T lymphocytes directed against HIV-infected targets. As HIV disease progresses, they are replaced by CD8+CD57+ suppressor cells. Virus-specific cytotoxic T lymphocytes secrete interferon-gamma (IFN-gamma ), an important cytokine in upregulating immune responses, primarily through macrophage activation. We examined the ability of lung and blood lymphocytes from HIV-positive patients at various stages of HIV infection to secrete IFN-gamma spontaneously and in response to phytohemagglutinin A. IFN-gamma production and secretion were determined with ELISA, Western blot, immunoprecipitation, and Northern blot techniques. Lung lymphocytes from HIV-infected individuals secreted large amounts of IFN-gamma . However, this ability was lost in patients with late-stage disease. Correlation between blood and lung lymphocyte IFN-gamma secretion was poor, suggesting regional differences in lymphocyte function. These data suggest that lung levels of IFN-gamma are high until late in HIV disease. These findings support the concept of administering exogenous IFN-gamma to patients with late-stage HIV disease and opportunistic infections.

lymphocytic alveolitis; cytotoxic T lymphocytes; suppressor cells; macrophage activation; human immunodeficiency virus





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