Protection Against Diabetes and Improved NK/NKT Cell Performance in NOD.NK1.1 Mice Congenic at the NK Complex

• Published in: The Journal of immunology (1950) Vol. 166; no. 4; pp. 2404 - 2411
• Main Authors: Carnaud, Claude, Gombert, Jean-Marc, Donnars, Olivier, Garchon, Henri-Jean, Herbelin, Andre
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.02.2001
• Subjects: Animals; Antigens - biosynthesis; Antigens, Ly; Antigens, Surface; Biomarkers - analysis; Cytotoxicity, Immunologic - genetics; Diabetes Mellitus, Type 1 - epidemiology; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - prevention & control; Female; Genetic Predisposition to Disease; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Lectins, C-Type; Mice; Mice, Congenic - genetics; Mice, Congenic - immunology; Mice, Inbred C57BL; Mice, Inbred NOD; NK Cell Lectin-Like Receptor Subfamily B; NK1.1 antigen; Prevalence; Protein Biosynthesis; Proteins; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.166.4.2404

The NK1.1 cell surface receptor, which belongs to the NKR-P1 gene cluster, has been bred onto nonobese diabetic (NOD) mice for two purposes. The first was to tag NK and NKT cells for easier experimental identification of those subsets and better analysis of their implication in type 1 diabetes. The second was to produce a congenic strain carrying Idd6, a susceptibility locus that has been repeatedly mapped in the vicinity of the NKR-P1 gene cluster and the NK complex, to explore the impact of this locus upon autoimmune diabetes. NOD.NK1.1 mice express the NK1.1 marker selectively on the surface of their NK and NKT cell subsets. In addition, the mice manifest reduced disease incidence and improved NK and NKT cell performance, as compared with wild-type NOD mice. The association of those two features in the same congenic strain constitutes a strong argument in favor of Idd6 being associated to the NK complex. This could explain at the same time the multiple alterations of innate immunity reported in NOD mice and the fact that disease onset can be readily modified by boosting the innate immune system of the mouse.