ANTIBODY TO THE LIGAND FOR CD40 (GP39) INHIBITS MURINE AIDS-ASSOCIATED SPLENOMEGALY, HYPERGAMMAGLOBULINEMIA, AND IMMUNODEFICIENCY IN DISEASE-SUSCEPTIBLE C57BL 6 MICE/

Infection of genetically susceptible C57BL/6 mice with the LP-BM5 isol ate of murine retroviruses causes profound splenomegaly, hypergammaglo bulinemia, lymphadenopathy, and an immunodeficiency syndrome which inc ludes the development of terminal B-cell lymphomas. Because many of th ese and the other manifestations of LP-BM5 virus-induced disease are s imilar to those seen in AIDS, this syndrome has been named murine AIDS , or MAIDS. Previous reports have shown that the onset of MAIDS depend s on the presence of both CD4(+) T cells and B cells and have suggeste d that CD4(+) T-cell-B-cell interactions are important to disease path ogenesis. 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 antib ody. As a result, MAIDS-associated splenomegaly, hypergammaglobulinemi a, germinal center formation, and the loss of in vitro responsiveness to the T- and B-cell mitogens concanavalin A and lipopolysaccharide we re inhibited. Anti-gp39 monoclonal antibody-treated LP-BM5-infected mi ce were also able to mount essentially normal alloantigen-specific cyt olytic T-lymphocyte responses. These results support the possibility t hat molecular interactions between CD40 and gp39 are critical to the d evelopment of MAIDS.