Anti–IL-21 mAb treatment decreases CD8⁺ T-cell numbers in xenogeneic GVHD and increases the percentage of CD4⁺ cells expressing Foxp3. NOD/SCID/γc^−/− mice receiving human HLA-A2⁻ PBMCs (30 × 10⁶ cells) were treated with anti–IL-21 mAb, isotype control antibody, or in vitro expanded, HLA-A2⁺ nTregs and were electively killed on days 10 and 20. Average number (± SEM) of human CD4⁺HLA-A2⁻ (A), CD8⁺HLA-A2⁻ (B) T cells in spleen or microliter of blood, or ratio of CD4/CD8 (gated for HLA-A2⁻) on day 20 (C). Relative (D) or total (E) number (× 10⁴; ± SEM) of human CD4⁺HLA-A2⁻Foxp3⁺ cells in spleen on day 10 or day 20. n = 3 or 4 mice for each time point (day 10 and day 20) and each treatment group, and data shown are representative of 2 independent experiments.