Extracellular lysosome‐associated membrane protein‐1 (LAMP‐1) mediates autoimmune disease progression in the NOD model of type 1 diabetes

Abstract

Treatment (from 5 to 25 weeks of age) with a novel blocking monoclonal antibody, mAb I-10, directed against the plasma membrane (pm) form of LAMP-1, protected against development of autoimmune diabetes in the NOD mouse. A shorter course of treatment, i.e. from 5 to 12 weeks of age, significantly reduced the occurrence of insulitis as well as disease onset. Interfering with pm-LAMP-1 required continuous treatment as tolerance was not observed when treatment was stopped, and no higher proportion of cells with a T regulatory phenotype (e.g. CD4 + CD25 + ) were induced. The mechanism appears to involve modulating a proinflammatory cytokine, as the proportion of pancreaticinfiltrating IFN-c-positive cells was significantly reduced in the mAb I-10-treated group. These results demonstrate an unexpected role for pm-LAMP-1 in autoimmune disease progression, and suggest that further investigation should be performed to understand how this molecule modulates IFN-c-driven responses.

Surface CD107a/LAMP-1 protects natural killer cells from degranulation-associated damage

“…Interestingly, a study by De Carvalho Bittencourt et al described an antibody against murine CD107a, which could reduce the occurrence of diabetes when injected into NOD mice. 43 This was associated with a reduction in IFNg-producing pancreatic infiltrating T cells. In light of our data, it is interesting to speculate that antibody-mediated blocking of CD107a may interfere with its protective effect and therefore result in the selective depletion of autoreactive lymphocytes during degranulation.…”