Fig. 9

Blocking mitochondrial fission enhances the efficacy of anti-CD3 mAb immunotherapy in autoimmune diabetic mice. A Experimental design for NY8.3 mice immunotherapy studies. Four-week-old female NY8.3 mice (n = 16/group) were treated with 10 µg anti-CD3mAb or 10 µg anti-CD3mAb in combination with O/A/M every day for 5 days or 20 µg IGRP_206–214 per nostril daily for 3 days. Mice were sacrificed at day 60 after treatment. B The prevalence of diabetes in NY8.3 mice during the course of treatment. C At day 60, the percentage of pancreatic islets exhibiting the specified histological scores in “non-diabetic” mice from A was measured. Representative pictures of the islets at day 60 “non-diabetic” mice from A. Scale bars, 50 μm. D TPEX, TEX, and total exhausted CD8⁺ T cells produced on day 60 were quantified and shown in flow cytograms (n = 8/group). E Experimental design for diabetic NY8.3 mice immunotherapy studies. Diabetic female NY8.3 mice (n = 16/group) were treated with 10 µg anti-CD3mAb or 10 µg anti-CD3mAb in combination with O/A/M every day for 5 days or 20 µg IGRP_206–214 per nostril daily for 3 days. Mice were sacrificed at day 30 after treatment. F The diabetes remission in diabetic NY8.3 mice after treatment. G On day 30, the percentage of pancreatic islets exhibiting the relevant histological score was measured in “non-diabetic” mice from E. Representative pictures of the islets at day 30 “non-diabetic” mice from E. H, I total exhausted CD8⁺ T cells, TPEX, and TEX cells produced on day 30 were quantified and shown in flow cytograms (n = 8/group). For insulitis, ten pieces per pancreas were blindly scored. (0 = no infiltrate, 1 = 0–25%, 2 = 25–75%, 3 ≥ 75%). White bars, 0; light grey bars, 1; dark grey bars, 2; black bars, 3. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. One-way ANOVA (B, D, F, I). Data represent two independent experiments. Scale bars, 50 μm