Anti-CD3 mAb treatment cures PDL1−/−.NOD mice of diabetes but precipitates fatal myocarditis

Anti-CD3 mAb is an effective therapy that can reverse diabetes in NOD mice and has therapeutic potential in patients with type 1 diabetes (T1D). We administered anti-CD3 to PDL1−/−.NOD mice in order to determine whether this treatment would reverse the development of diabetes in these mice. Mice injected with anti-CD3 mAb neonatally were protected from T1D. However, all of these anti-CD3 mAb treated PDL1−/−.NOD mice developed a wasting disease between 12 and 20 weeks of age with sudden deterioration and weight loss, leading to death within 3–5 days of development of illness. Histology revealed severe inflammation in the heart and skeletal muscles. These results suggest that deficiency of PDL1 in NOD background has the potential to lead to immune-mediated tissue damage in organs other than the pancreas, but this cannot be appreciated in PDL1−/−.NOD mice as the mice develop T1D at an early age and die from diabetes prior to manifesting other autoimmune diseases.

► Administration of anti-CD3 to neonatal PDL1−/−.NOD mice protected them from T1D. ► Interestingly, all of these anti-CD3 treated PDL1−/−.NOD mice developed a wasting disease between 12–20 weeks of age. ► This disease lead to sudden deterioration, weight loss and death within 3–5 days of development of illness. ► Histology revealed severe inflammation in the heart and skeletal muscles. ► Deficiency of PDL1 in NOD background has the potential to lead to immune-mediated tissue damage in heart.