ROLE OF ALVEOLAR MACROPHAGE T-CELL ADHERENCE IN ACCESSORY CELL-FUNCTION IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED INDIVIDUALS

Previous work has shown that alveolar macrophages (AM) from human immu nodeficiency virus (HIV)infected patients are superior accessory cells (AC) and secrete greater amounts of T cell-stimulatory cytokines than do normal AM, We now examine the role of AM-T cell adherence in AM AC function by examining the ability of beta 2 integrins and intercellul ar adhesion molecule-1 (ICAM-1) to block adherence and lymphoprolifera tion. Mitogen-induced (concanavalin A, pokeweed mitogen) adhesion and proliferation were studied in the presence and absence of mAb directed against beta 2 integrins and ICAM-1. AM from normal subjects and HIV- positive patients were used as AC, and normal T cells were used as res ponders. Normal and HIV AM bound equal numbers of T cells under simila r conditions. Adherence was blocked by antibodies to beta 2 integrins and ICAM-1 in both groups. Con A-induced lymphoproliferation was posit ively correlated with adherence in normal volunteers. In contrast, gre ater Con A-induced AM-T cell adherence in HIV-positive patients was as sociated with worse AC function. Antibodies that impaired AM-T cell ad herence completely inhibited AC function in both groups when added at the beginning of mitogen assays, indicating that initial contact was r equired. However, the addition of antibodies after 4 h inhibited lymph oproliferation less in HIV-infected individuals than in normal volunte ers, suggesting that prolonged AM-T cell adherence was less important for optimal AC function in these patients. Using these and previous re sults, we present a model for AM AC function in normal volunteers and HIV-infected individuals.