Figure 2.
IL-6 reprograms effector CD8+ T cells into IL-21–producing effector cells. (A) IL-2 production from CD8+ T cells activated using anti-CD3/CD28 Abs in the absence or presence of IL-6 for 72 h (n = 3). (B and C) Relative mRNA levels for IFN-γ (B) and IL-2 (C) in CD8+ T cells activated with or without IL-6 or IL-2. (D) Intracellular staining for IFN-γ and IL-2, and surface staining for hCD4 (surrogate for IL-21) on activated CD8+ IL-21-hCD4 reporter T cells. Numbers indicate the percentage of cells in each quadrant. (E and F) Percentage of different cytokine-producing populations as determined in D (n = 3). (G–I) CD8+ T cells were activated in the absence (primary, Med) or presence (primary, IL-6) of IL-6 for 2 d, harvested, and restimulated using anti-CD3 Ab in the absence (Restim, Med) or presence (Restim, IL-6) of IL-6. After 24 h, IL-21 production (G), the relative IL-21 mRNA levels (H), and IL-2 production (I) were determined (n = 3). (J and K) CD8+ T cells were activated with or without IL-6 that was added at the indicated time after activation. After 72 h of activation (J) and 72 h after the addition of IL-6 (K), IL-21 production was determined (n = 3). Error bars represent the mean ± SD. *, P < 0.05, as determined by Student’s t test (A), one-way ANOVA (B, C, J, and K), or two-way ANOVA (E–I). Results are representative of two to three experiments.