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

A CD8(+) lymphocytic alveolitis occurs in up to 60% of asymptomatic human i mmunodeficiency virus (HIV)-infected individuals. Early in HIV infection, l ymphocytes consist predominantly of cytotoxic T lymphocytes directed agains t 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 abilit y of lung and blood lymphocytes from HIV-positive patients at various stage s of HIV infection to secrete IFN-gamma spontaneously and in response to ph ytohemagglutinin A. IFN-gamma production and secretion were determined with ELISA, Western blot, immunoprecipitation, and Northern blot techniques. Lu ng 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 fi ndings support the concept of administering exogenous IFN-gamma to patients with late-stage HIV disease and opportunistic infections.