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 s imilarities to the human disease. NOD mice which are transgenic for the Ea gene, allowing expression of the E molecule, are protected from diabetes an d rarely develop insulitis, We have constructed bone marrow chimeras betwee n transgenic and non-transgenic NOD mice to study the correlation of E expr ession 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 chimera s 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 perip heral IL-4 production seen in NOD-E-->NOD, NOD-->NOD-E and NOD-->NOD chimer as correlates with the increased insulitis seen in these mice compared to N OD-E-->NOD-E. In contrast, there were no differences in IFN-gamma productio n between the chimeras, We suggest that the precommitted, regulatory T cell s, selected in an E-expressing thymic environment, need continuous interact ion with E-expressing primary antigen presenting cells in the periphery for optimal IL-4 production, Decrease in IL-4 production correlates with incre ased insulitis, iii 1999 Academic Press.