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. 2020 Nov 23;117(49):31319–31330. doi: 10.1073/pnas.2019743117

Fig. 7.

Fig. 7.

Decreasing the infiltration of MoMac into islets prevents diabetes following PD-1 blockade. (A) Flow cytometry analysis showing the effects of clodronate liposome treatment on islet myeloid cells. Results are representative of two independent experiments each with n ≥ 6 mice. (B) Ratio between MoMac and ReMac in islets from the data of A. Untreated age-matched NOD mice (n = 5) were examined as control. ***P = 0.0007, *P = 0.011, n.s., = 0.0874. (C) Percentage of infiltrating CD45 leukocytes from the data of A and B. ***P = 0.001, *P = 0.0496, n.s., = 0.0991. (D) Diabetes incidence of NOD mice treated with anti–PD-1 plus PBS liposomes (n = 13, red) or anti–PD-1 plus clodronate liposomes (n = 12, blue) at 6 to 8 wk of age. ****P < 0.0001. Results are pooled from three independent experiments. (E) Diabetes incidence of four strains of mice (NOD [n = 35, blue], NOD.IFNαR1−/− [n = 10, red], NOD.IFNγR1−/− [n = 17, green], and NOD.DKO [n = 13, purple]) treated with three injections of anti–PD-1. Ages of the mice ranged from 5-wk old to 16-wk old. Mice were followed for diabetes incidence for 4 wk. ****P < 0.0001, n.s., = 0.1363. Results are pooled from three independent experiments. (F) Diabetes incidence of NOD. Rag1−/− recipients (n = 14, red) or NOD. IFNγR1−/− Rag1−/− recipients (n = 17, blue) transferred with NOD splenocytes (107 per mouse). Four weeks later the mice were treated with three injections of anti–PD-1 antibodies and monitored diabetes for 4 wk. ***P = 0.0003. (G) Diabetes incidence of NOD mice treated with anti–PD-1 plus AG (6 mg per mouse, n = 13, blue) every 12 h for 20 d or anti–PD-1 alone (n = 9, red) starting at 5 to 7 wk of age and followed for 4 wk. **P = 0.004. Results are pooled from two independent experiments. (H) Flow cytometry analysis showing the effects of AG treatment: 5- to 7-wk-old NOD mice were treated as in G. Four weeks later, islets from the two groups of mice were isolated and examined by flow analysis. Data are representative from n = 4 mice from two independent experiments. Two mice from each group are combined for analysis in second experiment. (I) Ratio between MoMac and ReMac in islets from the data of H. (Ctrl vs. anti-PD-1) **P = 0.0026, (Ctrl vs. anti-PD-1+AG) **P = 0.0016, n.s., = 0.8421.