title: Antibody to the ligand for CD40 (gp39) inhibits murine AIDS-associated splenomegaly, hypergammaglobulinemia, and immunodeficiency in disease-susceptible C57BL/6 mice.
abstract: Infection of genetically susceptible C57BL/6 mice with the LP-BM5 isolate of murine retroviruses cause profound splenomegaly, hypergammaglobulinemia, lymphadenopathy, and an immunodeficiency syndrome which includes the development of terminal B-cell lymphomas. Because many of these and the other manifestations of LP-BM5 virus-induced disease are similar to those seen in AIDS, this syndrome has been named murine AIDS, or MAIDS. Previous reports have shown that the onset of MAIDS depends on the presence of both CD4+ T cells and B cells and have suggested that CD4+ T-cell-B-cell interactions are important to disease pathogenesis. Here, we assessed the possibility that interactions between CD40 and its ligand on activated CD4+ T cells, CD40 ligand/gp39, are involved in the development of MAIDS. To test this hypothesis, LP-BM5-infected B6 mice were treated in vivo with anti-gp39 monoclonal antibody. As a result, MAIDS-associated splenomegaly, hypergammaglobulinemia, germinal center formation, and the loss of in vitro responsiveness to the T- and B-cell mitogens concanavalin A and lipopolysaccharide were inhibited. Anti-gp39 monoclonal antibody-treated LP-BM5-infected mice were also able to mount essentially normal alloantigen-specific cytolytic T-lymphocyte responses. These results support the possibility that molecular interactions between CD40 and gp39 are critical to the development of MAIDS.
authors.affiliation: Department of Microbiology, Dartmouth Medical School, Lebanon, NH 03756, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Green
authors.forename: K M
authors.initials: KM
authors.lastname: Crassi
authors.forename: J D
authors.initials: JD
authors.lastname: Laman
authors.forename: A
authors.initials: A
authors.lastname: Schoneveld
authors.forename: R R
authors.initials: RR
authors.lastname: Strawbridge
authors.forename: T M
authors.initials: TM
authors.lastname: Foy
authors.forename: R J
authors.initials: RJ
authors.lastname: Noelle
authors.forename: W R
authors.initials: WR
authors.lastname: Green
mesh_terms: D000386:AIDS-Related Complex / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand; D006224:Cricetinae; D006942:Hypergammaglobulinemia / Q000209:etiology / Q000517:prevention & control; D007109:Immunity; D008024:Ligands; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology / Q000628:therapy*; D013154:Spleen / Q000473:pathology; D013163:Splenomegaly / Q000209:etiology / Q000517:prevention & control
chemical_list: D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand