| First Author | Maehr R | Year | 2005 |
| Journal | J Clin Invest | Volume | 115 |
| Issue | 10 | Pages | 2934-43 |
| PubMed ID | 16184198 | Mgi Jnum | J:101527 |
| Mgi Id | MGI:3604230 | Doi | 10.1172/JCI25485 |
| Citation | Maehr R, et al. (2005) Cathepsin L is essential for onset of autoimmune diabetes in NOD mice. J Clin Invest 115(10):2934-43 |
| abstractText | Lysosomal proteases generate peptides presented by class II MHC molecules to CD4+ T cells. To determine whether specific lysosomal proteases might influence the outcome of a CD4+ T cell-dependent autoimmune response, we generated mice that lack cathepsin L (Cat L) on the autoimmune diabetes-prone NOD inbred background. The absence of Cat L affords strong protection from disease at the stage of pancreatic infiltration. The numbers of I-A(g7)-restricted CD4+ T cells are diminished in Cat L-deficient mice, although a potentially diabetogenic T cell repertoire persists. Within the CD4+ T cell compartments of Cat L-deficient mice, there is an increased proportion of regulatory T cells compared with that in Cat L-sufficient littermates. We suggest that it is this displaced balance of regulatory versus aggressive CD4+ T cells that protects Cat L-deficient mice from autoimmune disease. Our results identify Cat L as an enzyme whose activity is essential for the development of type I diabetes in the NOD mouse. |
