Figure 6. A Subset of Th17 Cells Extinguish IL-17 and Transition to Single-Positive IFN-γ Cells in Transfer Model of Colitis.

(A and B) FACS-sorted CD4⁺CD45RB^hi T cells (4 ×10⁵) or CD4⁺CD45RB^lo (2 ×10⁵) T cells isolated from pooled spleen and LNs of Il17f^{Thy1.1/Thy1.1} mice were transferred into congenic Rag1^−/− mice as indicated. Th17-polarized T cells were generated from naive Il17f^{Thy1.1/Thy1.1} CD4⁺ T cells with Il12b^−/− APCs and anti-CD3 (2.5 μg/ml) as in Figure 1, in the absence (Th17 − IL-23) or presence (Th17 + IL-23) of 10 ng/ml IL-23. Thy1.1⁻ (IL-17F⁻ ) and Thy1.1⁺ (IL-17F⁺) cells were isolated by FACS sorting (see Figure S8), and 3 ×10⁵ cells were transferred as indicated. As shown in (A), 8 weeks after transfer, mice were sacrificed and intestinal tissues were collected for histological processing and analysis. Shown are representative sections of colon from indicated experimental groups; all magnifications represent 40×. (B) shows the incidence and severity of colitis 4 (upper panel) or 8 (lower panel) weeks after transfer of the indicated cell populations. n represents the number of recipients in each group.

(C and D) IL-17A, Thy1.1 (IL-17F), and IFN-γ expression of CD4⁺ T cells isolated from MLNs of indicated recipient mice 4 weeks (upper two panels) or 8 weeks (lower panel) after cell transfer. Recovered cells were stimulated ex vivo with PMA-ionomycin and analyzed for CD4, Thy1.1, and intracellular IL-17A and IFN-γ. Numbers in each quadrant indicate percentages of total CD4⁺ T cells (C). Cumulative data for frequencies of cytokine-positive CD4⁺ T cells, as analyzed as in (C), are shown in (D). Data are the means ± SEM for tissues and groups indicated. All data are representative of results from five similar experiments.