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-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.

Ämnesord

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Nyckelord

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

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)