Cathepsin L is essential for onset of autoimmune diabetes in NOD mice
AuthorMaehr, R; Mintern, JD; Herman, E; Lennon-Dumenil, AM; Mathis, D; Benoist, C; Ploegh, HL
Source TitleJournal of Clinical Investigation
PublisherAMER SOC CLINICAL INVESTIGATION INC
University of Melbourne Author/sMintern, Justine
AffiliationMicrobiology And Immunology
Document TypeJournal Article
CitationsMaehr, R., Mintern, J. D., Herman, E., Lennon-Dumenil, A. M., Mathis, D., Benoist, C. & Ploegh, H. L. (2005). Cathepsin L is essential for onset of autoimmune diabetes in NOD mice. JOURNAL OF CLINICAL INVESTIGATION, 115 (10), pp.2934-2943. https://doi.org/10.1172/JCI25485.
Access StatusAccess this item via the Open Access location
Open Access at PMChttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1224301
C1 - Journal Articles Refereed
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.
KeywordsCellular Immunology; Immune System and Allergy
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