Abstract
Autoimmune diabetes is characterized by inflammatory infiltration; however, the initiating events are poorly understood. We found that the islets of Langerhans in young nonobese diabetic (NOD) mice contained two antigen-presenting cell (APC) populations: a major macrophage and a minor CD103(+) dendritic cell (DC) population. By 4 weeks of age, CD4(+) T cells entered islets coincident with an increase in CD103(+) DCs. In order to examine the role of the CD103(+) DCs in diabetes, we examined Batf3-deficient NOD mice that lacked the CD103(+) DCs in islets and pancreatic lymph nodes. This led to a lack of autoreactive T cells in islets and, importantly, no incidence of diabetes. Additional examination revealed that presentation of major histocompatibility complex (MHC) class I epitopes in the pancreatic lymph nodes was absent with a partial impairment of MHC class II presentation. Altogether, this study reveals that CD103(+) DCs are essential for autoimmune diabetes development.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antigen Presentation / immunology
-
Antigens, CD / biosynthesis*
-
Autoimmunity / immunology
-
Basic-Leucine Zipper Transcription Factors / genetics*
-
CD8 Antigens / biosynthesis*
-
Diabetes Mellitus, Type 1 / genetics
-
Diabetes Mellitus, Type 1 / immunology*
-
Epitopes / biosynthesis
-
Epitopes / immunology
-
Female
-
Histocompatibility Antigens Class I / biosynthesis
-
Histocompatibility Antigens Class I / immunology
-
Histocompatibility Antigens Class II / biosynthesis
-
Histocompatibility Antigens Class II / immunology
-
Homeodomain Proteins / genetics
-
Inflammation / immunology
-
Integrin alpha Chains / biosynthesis*
-
Islets of Langerhans / cytology
-
Islets of Langerhans / immunology
-
Langerhans Cells / immunology*
-
Lymph Nodes / cytology
-
Macrophages / immunology
-
Mice
-
Mice, Inbred NOD
-
Mice, Knockout
-
Pancreas / cytology
-
Repressor Proteins / genetics*
-
T-Lymphocytes / immunology
Substances
-
Antigens, CD
-
Basic-Leucine Zipper Transcription Factors
-
CD8 Antigens
-
CD8alpha antigen
-
Epitopes
-
Histocompatibility Antigens Class I
-
Histocompatibility Antigens Class II
-
Homeodomain Proteins
-
Integrin alpha Chains
-
Repressor Proteins
-
SNFT protein, mouse
-
alpha E integrins
-
RAG-1 protein