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

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-γ (IFN-γ), 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-γ spontaneously and in response to phytohemagglutinin A. IFN-γ 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-γ. However, this ability was lost in patients with late-stage disease. Correlation between blood and lung lymphocyte IFN-γ secretion was poor, suggesting regional differences in lymphocyte function. These data suggest that lung levels of IFN-γ are high until late in HIV disease. These findings support the concept of administering exogenous IFN-γ to patients with late- stage HIV disease and opportunistic infections.