The AIDS disease of CD4C/HIV transgenic mice shows impaired germinal centers and autoantibodies and develops in the absence of IFN-gamma and IL-6

The mechanisms responsible for degeneration of germinal centers (GC) and fo llicular dendritic cell (FDC) networks during progression to AIDS remain el usive. Here, we show that CD4(+) T cells from CD4C/HIV-1 Tg mice, which dev elop a severe AIDS-like disease, express low levels of CD40 ligand. Accordi ngly, GC formation, FDC networks, and immunoglobulin isotype switching are impaired in these animals. However, Tg B cells respond to in vitro CD40 sti mulation. Total serum IgG levels are reduced in Tg mice, whereas total IgM levels are increased with a significant amount showing DNA specificity. IFN -gamma- and IL-6-deficient CD4C/HIV-1 Tg mice also develop the AIDS-like di sease and produce auto-Ab. Thus, CD4C/HIV-1 Tg mice have immune dysfunction accompanied by autoimmune responses.