FIGURE 3. Local inflammation in pancreas can induce the reprogramming of Th17 cells into Th1 cells.

(A) Purified in vitro differentiated BDC2.5 Th17 cells were transferred into NOD.Scid recipients (0.5×10⁶/recipient). At different time points after cell transfer, mononuclear cells recovered from pancreata were enumerated (right panel). Cytokine production of donor cells was analyzed by intracellular staining and FACS; the ratios between IFNγ⁺ and IL-17⁺ cells were calculated (left panel). Three to four recipients were analyzed at each time point in the same experiment. (B) Purified in vitro differentiated WT (polyclonal, Thy1.1) Th17 cells were transferred into NOD.Scid recipients (0.5×10⁶ per recipient) alone, or 2 days after a pre-transfer of BDC2.5 Th1 cells (Thy1.2, 0.2×10⁶). Pancreas samples were harvested 5 days after Th17 cell transfer, fixed and analyzed by histology using H&E staining. Shown are representatives of 3 recipients per group. (C) Th17 cells and Th1 cells were generated and transferred to NOD.Scid recipients as in (B). Recipients of Th17 alone were analyzed 14 days after cell transfer. Recipients given Th17 cells after BDC2.5 Th1 cells were analyzed 11 days after Th1 transfer, when diabetes was diagnosed. Donor cells were recovered and analyzed for cytokine expression. Th17 and Th1 cells were distinguished by Thy1.1 vs Thy1.2 staining, respectively. Shown are representative FACS plots of 5 recipients per group in two experiments.