Figure 7.

Autoreactive OT-3 T cells differentiate into normal effector and memory T cells. (A) Lethally irradiated Rip-mOva or C57BL/6 mice were reconstituted as described in Fig. 4. 6 wk later, expression levels of CD5, CD44, CD25, and PD-1 on OT-3 T cells in C57BL/6 mice (termed foreign-OT-3) and in Rip-mOva mice (self–OT-3 T cells) were determined (representative data for n = 5 mice per group are shown). The black line represents the level of CD5 expression by endogenous T cells. The data are representative of two experiments. (B) Similar chimeric mice were infected at 11 wk after reconstitution with Lm-Ova and, 7 d later, splenocytes were stained with GrzB, anti-CD127, and anti-KLRG1. They were also restimulated with SIINFEKL peptide and then stained intracellularly for IFN-γ and TNF. Shown are OT-3 gated flow cytometry plots representative of n = 3 mice per group. The dashed lines on the left are endogenous CD8⁺ T cells. (C) Rip-mOva mice received 5 × 10⁴ foreign– or self–OT-3 T cells (described in A), and blood glucose levels and T cell expansion were determined after an Lm-Ova infection (n = 5 mice per group). Values >200 mg/dl were considered diabetic. The experiments shown in B and C were performed two times and showed a similar outcome. (D) H-2K^bm1/Rip-mOva mice were lethally irradiated and grafted with C57BL/6 bone marrow. 8 wk after the reconstitution, 5 × 10⁴ OT-3 Rag2^−/− T cells were injected and the mice were infected with Lm-Ova. The frequency of OT-3 T cells was determined 6 and 28 d after the Lm-Ova infection and at day 6 after a VSV-Ova rechallenge. The data are pooled from two independently performed experiments with n = 3 mice per group and experiment. The horizontal bars in C and D represent the mean value of the individual data points.