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 immunodeficiency 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 intercellular adhesion molecule-1 (ICAM-1) to block adherence and lymphoproliferation. 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 responders. Normal and HIV AM bound equal numbers of T cells under similar conditions. Adherence was blocked by antibodies to beta 2 integrins and ICAM-1 in both groups. Con A-induced lymphoproliferation was positively correlated with adherence in normal volunteers. In contrast, greater Con A-induced AM-T cell adherence in HIV-positive patients was associated with worse AC function. Antibodies that impaired AM-T cell adherence completely inhibited AC function in both groups when added at the beginning of mitogen assays, indicating that initial contact was required. However, the addition of antibodies after 4 h inhibited lymphoproliferation less in HIV-infected individuals than in normal volunteers, suggesting that prolonged AM-T cell adherence was less important for optimal AC function in these patients. Using these and previous results, we present a model for AM AC function in normal volunteers and HIV-infected individuals.
Twigg
H L
HL
Department of Medicine, Indiana University Medical Center, Indianapolis 46202.
Soliman
D M
DM
D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000032:analysis; D018821:CD18 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D002478:Cells, Cultured; D015658:HIV Infections / Q000276:immunology*; D006679:HIV Seropositivity / Q000276:immunology*; D006801:Humans; D016023:Integrins / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1; D008213:Lymphocyte Activation; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D011043:Pokeweed Mitogens; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016023:Integrins; D011043:Pokeweed Mitogens; D018799:Intercellular Adhesion Molecule-1