CD28-B7 COSTIMULATORY BLOCKADE BY CTLA4IG DELAYS THE DEVELOPMENT OF RETROVIRUS-INDUCED MURINE AIDS

Mouse AIDS (MAIDS) induced in C57BL/6 mice by infection with a replica tion-defective retrovirus (Du5H) combines extensive lymphoproliferatio n and profound immunodeficiency. Although B cells are the main target of viral infection, recent research has focused on CD4(+) T cells, the activation of which is a key event in MAIDS induction and progression . A preliminary observation of increased expression of B7 molecules on B cells in MAIDS prompted us to address the possible involvement of t he CD28/B7 costimulatory pathway in MAIDS. Mice infected with the MAID S-inducing viral preparation were treated with murine fusion protein C TLA4Ig (3 x 50 mu g/week given intraperitoneally), a competitive inhib itor of physiological CD28-B7 interactions. In CTLA4Ig-treated animals , the onset of the disease was delayed, lymphoproliferation progressed at a much slower rate than in untreated mice, and the loss of in vitr o responsiveness to mitogens was reduced. Relative expression of Du5H did not differ between treated and untreated animals. These results su ggest that the CD28/B7 costimulatory pathway contributes to MAIDS deve lopment.