FIGURE 1.

IL-6–mediated reversal of Treg function requires activation of pStat3. CD4⁺CD25^– T cells and CD4⁺CD25^high Tregs were isolated from peripheral blood of healthy donors. Cells were cultured alone or together for 7 d at a 1:1 ratio with irradiated, allogeneic APCs in MLRs. Proliferation was assessed by titrated thymidine [³H] incorporation during the final 16 h of the 7-d assay. A and B, Cells were cocultured with or without 100 ng/ml rhIL-6 and indicated concentrations of Stattic V, an inhibitor of activated Stat3. C, Cells were cocultured with or without 100 ng/ml rhIL-6 and 50 ng/ml Stattic V, a peptide inhibitor of Stat3, an inactive peptide control, or Stat inhibitor VII. All experiments (A–C) were supplemented with 25 ng/ml sIL-6Rα. Three separate experiments were performed for each of A, B, and C, and data from one representative experiment are shown. Each individual experiment was internally significant where indicated (six cell culture replicates for each condition ± SEM), and p values were adjusted using the Bonferroni method.