Loss of CD4⁺IL-21⁺ T cells is associated with preferential depletion of Th17 cells and increased T-cell proliferation in chronically SIV-infected RMs. (A) Positive correlation between the absolute level of CD4⁺IL-21⁺ T cells (expressed as number per microliter) and the percentages of Th17 cells in blood. (B) Positive correlation between the absolute levels of intestinal CD4⁺IL-21⁺ T cells in rectal mucosa (expressed as percentage of total CD3⁺) and the percentages of Th17 cells in rectal mucosa. In blood, the percentage of CD4⁺IL-21⁺ T cells correlated directly with the percentage of CD4⁺ T cells (C) and inversely with the percentage of proliferating (Ki-67⁺) CD8⁺ T cells (D). At the level of intestinal mucosa, the percentage of CD4⁺IL-21⁺ T cells correlated negatively with the percentage of intestinal CD4⁺Ki-67⁺ (E) and CD8⁺Ki-67⁺ (F) T cells. (G) Three chronically SIV-infected RMs (day 380 after infection) were treated in vivo with 5 weekly doses of IL-21. Percentages of CD4⁺IL-17⁺ (left panel) and CD4⁺IL-17⁺IL-21⁺ (right panel) T cells were compared before and after IL-21 treatment. Numbers close to the symbols indicate fold increase compared to baseline.