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
1999 (English)In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 11, no 10, 766-772 p.Article in journal (Refereed) Published
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-γ. 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-γ 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.
Place, publisher, year, edition, pages
1999. Vol. 11, no 10, 766-772 p.
Bone marrow chimeras, Diabetes, IL-4, NOD-E, cytokine, gamma interferon, interleukin 4, animal cell, animal experiment, animal model, animal tissue, antigen presenting cell, article, bone marrow cell, chimera, controlled study, cytokine production, female, gene expression, insulin dependent diabetes mellitus, insulitis, mouse, nonhuman, priority journal, t lymphocyte, thymocyte, transgene, Animals, B-Lymphocytes, Bone Marrow Cells, Bone Marrow Transplantation, Diabetes Mellitus, Type 1, Epithelial Cells, Histocompatibility Antigens Class II, Inflammation, Interferon Type II, Interleukin-4, Islets of Langerhans, Male, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, Transgenic, Radiation Chimera, Spleen, Thymus Gland, Animalia
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:sh:diva-22922DOI: 10.1006/cyto.1998.0482ISI: 000082855700006PubMedID: 10525315ScopusID: 2-s2.0-0032823096OAI: oai:DiVA.org:sh-22922DiVA: diva2:710637