Antiapoptotic effects of IL-15 on pulmonary Tc1 cells of patients with human immunodeficiency virus infection

In the early phases of human immunodeficiency virus (HIV) disease a T-cell alveolitis sustained by cytotoxic T lymphocytes (CTL) with anti-HIV activit y occurs in the lung. With the progression of HIV disease, pulmonary CTL be come infected and their cytotoxic activity declines. To investigate the pot ential causes leading to this phenomenon, we evaluated T cells obtained fro m the bronchoalveolar lavage (BAL) of 18 HIV-infected patients with T-cell alveolitis. BAL T cells were CD45RO+/CD8+ defined as Tc1 cells because they expressed cytoplasmic interferon gamma (IFN-gamma) and were CXCR3+/IL-12R beta2+. Furthermore, they bore the interleukin (IL)-15 receptor, Fas antige n, and tumor necrosis factor receptor (TNFR) type II. When cultured for 24 h highly purified BAL T cells showed an excessive spontaneous apoptosis; af ter activation with anti-CD3 or ionomycin, the proportion of T cells underg oing cell death increased. Interestingly, we found a direct relationship be tween the predisposition to undergo spontaneous apoptosis and the levels of Fas expression by BAL T cells. Alveolar macrophages (AMs) expressed high l evels of IL-15 which paralleled the intensity of T-cell infiltration in mos t patients. The predisposition of CD8 T cells to undergo cell death was dow nregulated by the incubation with IL-15; the protective effect of the cytok ine was dose-dependent. Nonetheless, AMs also expressed proapoptotic molecu les, including membrane TNF-alpha (mTNF-alpha). Based on these observations it may be suggested that an excessive, spontaneous, and activation-induced apoptosis of pulmonary lymphocytes may be observed in HIV lung and that AM s are major regulators of T-cell homeostasis.