E expression is needed on both bone marrow derived cells and thymic epithelium to increase IL-4 production and achieve protection in NOD bone marrow chimeras.
The NOD mouse is an animal model for insulin-dependent diabetes with many similarities to the human disease. NOD mice which are transgenic for the Ea gene, allowing expression of the E molecule, are protected from diabetes and rarely develop insulitis. We have constructed bone marrow chimeras between transgenic and non-transgenic NOD mice to study the correlation of E expression on bone marrow derived cells and thymic epithelium vs the production of IL-4 and IFN-gamma. We show that NOD-E-->NOD-E and NOD-E-->NOD chimeras have elevated levels of IL-4 compared to NOD-->NOD and NOD-->NOD-E chimeras in the thymus. However, in the periphery the protected NOD-E-->NOD-E show much higher IL-4 levels than any of the other chimeras. This drop in peripheral IL-4 production seen in NOD-E-->NOD, NOD-->NOD-E and NOD-->NOD chimeras correlates with the increased insulitis seen in these mice compared to NOD-E-->NOD-E. In contrast, there were no differences in IFN-gamma production between the chimeras. We suggest that the precommitted, regulatory T cells, selected in an E-expressing thymic environment, need continuous interaction with E-expressing primary antigen presenting cells in the periphery for optimal IL-4 production. Decrease in IL-4 production correlates with increased insulitis.
Brenden
N
N
Department of Immunology, Wenner-Gren Institute, Arrhenius Laboratories for Natural Sciences, Stockholm University, Stockholm, S-106 91, Sweden.
Rietz
C
C
Böhme
J
J
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology / Q000473:pathology; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D011828:Radiation Chimera / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D015847:Interleukin-4; D007371:Interferon-gamma