Disease‐protected major histocompatibility complex Ea‐transgenic non‐obese diabetic (NOD) mice show interleukin‐4 production not seen in susceptible Ea‐transgenic and non‐transgenic NOD mice

• Published in: Immunology Vol. 95; no. 1; pp. 1 - 7
• Main Authors: Brenden, N, Boehme, J
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.09.1998
• Subjects: animal cell; animal experiment; animal model; animal tissue; Animals; cd4 antigen; cd8 antigen; Cells; Cells, Cultured; controlled study; Cultured; Diabetes Mellitus; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; disease predisposition; Enzyme-Linked Immunosorbent Assay; gamma interferon; Gene Expression; gene mutation; Genetic Predisposition to Disease; Histocompatibility Antigens Class I; Histocompatibility Antigens Class I - genetics; HLA Antigens; HLA Antigens - genetics; HLA-E Antigens; Inbred NOD; insulin dependent diabetes mellitus; insulitis; Interferon Type II; Interferon-gamma - biosynthesis; Interleukin-4; Interleukin-4 - analysis; Interleukin-4 - biosynthesis; Interleukin-4 - genetics; major histocompatibility antigen class 2; major histocompatibility complex; Medicin och hälsovetenskap; Messenger; messenger rna; Mice; Mice, Inbred NOD - genetics; Mice, Inbred NOD - immunology; Mice, Transgenic; mouse; nonhuman; priority journal; promoter region; protection; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger - analysis; Spleen; Spleen - immunology; t lymphocyte; T-Lymphocytes; T-Lymphocytes - immunology; Thymus Gland; Thymus Gland - immunology; Transgenic; transgenic mouse; Type 1
• ISSN: 0019-2805; 1365-2567; 1365-2567
• DOI: 10.1046/j.1365-2567.1998.00580.x

The non‐obese diabetic (NOD) mouse is an animal model for insulin‐dependent diabetes that has many similarities to the human disease. NOD mice transgenic for the Ea gene, allowing expression of the E molecule, are protected from diabetes and rarely develop insulitis. An Ea transgene mutated in the promoter region, (ΔY) lacks E expression on most B cells, thymic medullary epithelium and primary antigen‐presenting cells, and confers no protection whatsoever. We have used these transgenic NOD mice, together with non‐transgenic NOD mice, to study the correlation of E expression and production of interleukin‐4 (IL‐4) and interferon‐γ (IFN‐γ). We show that protected E‐transgenic NOD mice have elevated levels of IL‐4 compared with non‐transgenic mice, both in the thymus and in the periphery. However, susceptible ΔY‐transgenic mice have elevated thymic IL‐4 levels, but express almost as little IL‐4 as non‐transgenic NOD mice in the periphery. This drop in peripheral IL‐4 production seen in ΔY‐transgenic mice thus correlates with the decreased E expression in the periphery of ΔY‐transgenic NOD mice. In contrast, there were no differences in IFN‐γ production between the three NOD lines. We suggest that Ea‐transgenic NOD mice have E‐selected regulatory T cells producing IL‐4, which are subsequently activated by E‐expressing primary antigen‐presenting cells in the periphery. This activation would then be instrumental for the E‐mediated protection from disease in NOD mice. Such a process would explain the total absence of protection in ΔY‐transgenic NOD mice, despite their widespread E expression.