Antibody blockade of the IL-6R augments conversion of CD4⁺ foxp3⁻ to CD4⁺ foxp3⁺ Tregs. Lethally irradiated (900 cGy) Balb/c mice received a transplant of B6 Rag-1 BM (5 × 10⁶) and sorted CD4⁺ EGFP-foxp3⁻ T cells (0.2 × 10⁶). Cohorts of mice were then administered rat IgG isotype control (n = 9) or anti–IL-6R antibody (n = 12) once weekly for 4 weeks as described in “Methods.” Mice in both groups were killed 26 to 36 days after transplantation. (A) Pathological damage in the colon, liver, and lung using a semiquantitative scoring system as detailed in “Histologic analysis.” (B) Total spleen cellularity and (C) absolute number of splenic CD4⁺ T cells are depicted. (D) Representative dot plot showing percentage of EGFP-foxp3⁺ iTregs in the gated CD4⁺ T-cell population from transplant recipients treated with either isotype control or anti–IL-6R antibody. (E) Percentage and (F) absolute number of iTregs in the spleen of animals administered control or anti–IL-6R antibody. Data are presented as the mean (± SEM) and are the cumulative results from 3 independent experiments. (Statistics: *P ≤ .05, **P < .01.)