title: Enhancement of innate and cell-mediated immunity by antimycobacterial antibodies.
abstract: We investigated the ability of human antibodies induced by Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination to protect against mycobacterial infections. Serum samples containing mycobacterium-specific antibodies were obtained from volunteers who had received two intradermal BCG vaccinations 6 months apart. Significant increases in lipoarabinomannan (LAM)-specific immunoglobulin G (IgG) were detected after both the primary and booster vaccinations. Effects of mycobacterium-specific antibodies on surface binding and internalization of BCG by neutrophils and monocytes/macrophages were studied, using green fluorescent protein (gfp)-expressing BCG. Surface-bound gfp-expressing BCG were distinguished from intracellular BCG by surface labeling with LAM-specific monoclonal antibody. Internalization of BCG by phagocytic cells was shown to be significantly enhanced in postvaccination serum samples. Furthermore, the inhibitory effects of neutrophils and monocytes/macrophages on mycobacterial growth were significantly enhanced by BCG-induced antibodies. The growth-inhibiting effects of postvaccination sera were reversed by preabsorption of IgG with Protein G. Finally, the helper effects of antimycobacterial antibodies for the induction of cell-mediated immune responses were investigated. BCG-induced antibodies significantly enhanced proliferation and gamma interferon production in mycobacterium-specific CD4(+) and CD8(+) T cells, as well as the proportion of proliferating and degranulating CD8(+) T cells. We conclude that mycobacterium-specific antibodies are capable of enhancing both innate and cell-mediated immune responses to mycobacteria.
authors.affiliation: Department of Internal Medicine, Saint Louis University Health Science Center, MO 63110, USA.
authors.forename: S
authors.initials: S
authors.lastname: de Vallière
authors.forename: G
authors.initials: G
authors.lastname: Abate
authors.forename: A
authors.initials: A
authors.lastname: Blazevic
authors.forename: R M
authors.initials: RM
authors.lastname: Heuertz
authors.forename: D F
authors.initials: DF
authors.lastname: Hoft
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000737:chemistry / Q000382:microbiology; D009000:Monocytes / Q000737:chemistry / Q000382:microbiology; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology*; D009504:Neutrophils / Q000737:chemistry / Q000382:microbiology; D010587:Phagocytosis / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*
chemical_list: D000907:Antibodies, Bacterial; D001500:BCG Vaccine; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; C050016:lipoarabinomannan; D049452:Green Fluorescent Proteins