Tolerogenic function of gp120 in vivo is regulatory T-cell-dependent. (A) 107 Treg-depleted PBMC with or without 5 μg gp120 were injected into newborn NOD-Scid mice. Untreated mice served as controls. Each point represents the cumulative mean weight data of 5 mice per group (1 of 5 experiments is shown). Bars represent SEM. Survival of mice at day 43: untreated: 5/5; CD25-depleted PBMC: 0/5; and CD25-depleted PBMC + gp120: 0/5. (B) GTP serum levels of mice belonging to different groups 3 weeks after PBMC transfer. (C) Inhibition of adenylate cyclases in Tregs abrogates the tolerogenic function of gp120 in vivo. PBMCs (107) containing 3% syngenic Tregs either left untreated (Tregs) or pretreated with the adenylate cyclase inhibitor MDL-12 (50μM) for 30 minutes (Tregs*) were injected into newborn NOD-Scid mice with or without 5 μg gp120. Untreated mice served as controls. Each point represents the cumulative mean weight data of 3 mice per group (1 of 2 experiments is shown). Bars represent SEM. Survival of mice at day 52: untreated: 5/5; PBMC with untreated Tregs: 0/5; PBMC with untreated Tregs + gp120: 5/5; PBMC with MDL-12–treated Tregs: 0/5; and PBMC with MDL-12–treated Tregs + gp120: 0/5.
