Figure 2. Paradoxical protective effect of diabetogenic T cells in autoimmune diabetes.

(A) Diabetes incidence in ins-HA mice after transfer of freshly purified HA-Teffs (white circles, n = 13) or preactivated HA-Teffs (black circles, n = 9) or expanded HA-Tregs (white squares) or coinjection of preactivated HA-Teffs and expanded HA-Tregs (white triangles, n = 9). Data were from 4 experiments. (B) Ins-HA mice were transferred with expanded HA-Tregs alone (white squares, n = 12) or with preactivated HA-Teffs (white triangles, n = 21). 3 weeks later (arrow), mice were challenged for diabetes induction with preactivated HA-Teffs. Data were from 4 independent experiments. (C) Ins-HA mice were cotransferred with expanded HA-Tregs and the CD4⁺ (white triangles, n = 14) or CD4^– (black diamonds, n = 12) fractions of preactivated HA-Teffs. Mice were challenged 3 weeks later (arrow) with preactivated HA-Teffs. Data were from 2 independent experiments. (D and E) Ins-HA mice were transferred with 20 × 10⁶ expanded HA-Tregs alone (black squares, n = 4) or coinjected with 2 × 10⁶ expanded HA-Tregs and 2 × 10⁶ preactivated HA-Teffs (white triangles, n = 21) or injected with PBS only (for E). Mice were challenged 3 weeks later with preactivated HA-Teffs to test their susceptibility to diabetes induction (D) or with CFSE-labeled Thy-1.1⁺ preactivated HA-Teffs to analyze their activation 4 days later in PLNs (E). (E) CFSE profile and IFN-γ production of CD4⁺Thy-1.1⁺FoxP3^– cells (left panels) and quantification of CD4⁺Thy-1.1⁺FoxP3^–IFNγ⁺ cell numbers (right panel). In A–D, Teffs and Tregs were obtained from Thy-1.2 TCR-HA mice. Data were from 6 mice per group from 2 independent experiments. *P < 0.05; **P < 0.001. Error bars represent SD.