1. Abundance of non–islet-specific CTLs at islets is immune-suppressive.
Abundance of non–islet-specific CTLs at islets is immune-suppressive. (A and C) Adoptive transfer of equal amounts (1 × 106) of P14 and OT-I CD8+ T cells resulted in an abundance of non–islet-specific OT-I CTLs at islets on day 9 in RIP-GP mice (A) compared with when the ratio was changed to 1000:1 (P14:OT-I) (C). (B and D) Follow-up studies of the mice on day 16 showed that the infiltrate was gone, and in the HI (1:1 ratio) group, the islets were found to be mostly intact (B), whereas in the LO (1000:1 ratio) group, very few β cells were found (D). Scale bars, 30 μm. (E) A majority of the HI group (six of eight) displayed normoglycemia, whereas only one of eight was normoglycemic in the LO group (*P = , 1:1 versus 1:1000, log-rank test). Different ratios of cell transfers suggested a dose-dependent mechanism because 50% of the mice in the group receiving a 10:1 ratio remained normoglycemic. (F to H) These scenarios were repeated in three different transgenic models that express model Ags on β cells: RIP-GP (six of eight were normoglycemic, representative of four independent experiments) (F), RIP-mOVA (five of six were normoglycemic, representative of two independent experiments) (G), and RIP-OVAlow (three of four were normoglycemic, representative of two independent experiments) (H).
Gustaf Christoffersson et al. Sci. Immunol. 2018;3:eaam6533
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