Pulmonary morbidity and mortality due to opportunistic infection is a prominent feature of the acquired immunodeficiency syndrome (AIDS). One potential explanation for the high frequency of respiratory tract involvement in AIDS would be localized impairment of immunocompetence. The demonstrated susceptibility of alveolar macrophages to infection with human immunodeficiency virus (HIV), and reports of functional abnormalities in alveolar macrophage populations derived from patients with AIDS, suggest that altered alveolar macrophage function could lead to impaired pulmonary immunity in AIDS. These studies will investigate the relationships between in vivo pulmonary immune function, in vivo infection of alveolar macrophages by HIV, and alveolar macrophage immunomodulatory function in vitro. In vivo pulmonary immune function will be assessed by transbronchoscopic instillation of keyhole limpet hemocyanin (KLH) into a single lingular segment, with subsequent monitoring of specific humoral immune responses in peripheral blood. Severity of in vivo alveolar macrophage infection with HIV, and assessment of alveolar macrophage immunomodulatory function in vitro, will be determined using bronchoalveolar lavage (BAL) cell populations obtained from the right middle lobe just prior to immunization of the lingula. In aggregate, these studies will: 1. Elucidate the immunoglobulin class-specific effects of HIV infection on humoral responses to primary lung immunization; 2. Compare the ability of lymphocyte subset analysis in peripheral blood and BAL to predict responses to lung immunization in HIV- infected individuals; 3. Evaluate the effect of alveolar macrophage infection with HIV on responses to lung immunization in vivo; and 4. Assess the relationships between alveolar macrophage expression of HLA-DR, alveolar macrophage production of the cytokines interleukin-1 and tumor necrosis factor, and specific immunity to intrapulmonary antigen in vivo. Thus, these studies will clarify the relationships between HIV infection, alveolar macrophages, and functional pulmonary immunity in AIDS.
| Weissman, D N; Bice, D E; Crowell, R E et al. (1994) Intrapulmonary antigen deposition in the human lung: local responses. Am J Respir Cell Mol Biol 11:607-14 |
