Mechanism underlying counterregulation of autoimmune diabetes by IL-4.
Diabetes in nonobese diabetic (NOD) mice is an autoimmune disease characterized by the destruction of the beta cells in the pancreas. We have previously reported that transgenic expression of interleukin-4 (IL-4) counterregulates the disease process, completely protecting NOD mice from insulitis and diabetes. Here we demonstrate the presence of autoreactivity but lack of pathogenicity of the IL-4-regulated lymphocytes. The importance of T cell diversity for the protective effect of IL-4 is demonstrated through breeding with transgenic BDC2.5 mice, which have an almost exclusively monoclonal T cell repertoire. Limitation of T cell diversity abrogated the protection by IL-4. We suggest that "immune deviation" in NOD-IL-4 mice is mediated by the pancreatic tissue itself, which causes activation of distinct, nonpathogenic T cell specificities.
Mueller
R
R
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Bradley
L M
LM
Krahl
T
T
Sarvetnick
N
N
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003520:Cyclophosphamide / Q000633:toxicity; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D007108:Immune Tolerance; D015847:Interleukin-4 / Q000276:immunology* / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology
D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D003520:Cyclophosphamide