Variable effects of transgenic c-Maf on autoimmune diabetes.
Autoimmune diabetes is associated with T helper 1 polarization, but protection from disease can be provided by the application of T helper 2 (Th2) cytokines. To test whether genetic manipulation of T-cells can provide protective Th2 responses, we developed transgenic mice in which T-cells express the interleukin-4-specific transcription factor c-Maf. When crossed with a transgenic model that combines a class II restricted T-cell receptor specific for influenza hemagglutinin with islet beta-cell expression of hemagglutinin, the c-Maf transgene provided significant protection from spontaneous autoimmunity but not from adoptively transferred diabetes. In a second transgenic model in which islet cells express the lymphocytic choriomeningitis virus nucleoprotein, the virus infection triggers autoimmune diabetes within a few weeks involving both CD4 and CD8 T-cells; here too transgenic c-Maf provided significant protection. Surprisingly, when the c-Maf transgene was backcrossed with the NOD model of spontaneous disease, no protection was evident. Thus, transgenic c-Maf can strongly influence autoimmune disease development in some models, but additional factors, such as background genetic differences, can influence the potency of its effect.
Pauza
M E
ME
Department of Immunology, The Scripps Research Institute, La Jolla, California, USA.
Nguyen
A
A
Wolfe
T
T
Ho
I C
IC
Glimcher
L H
LH
von Herrath
M
M
Lo
D
D
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation; D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000494:pharmacology*; D003920:Diabetes Mellitus / Q000235:genetics / Q000473:pathology / Q000517:prevention & control / Q000821:virology; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology; D008216:Lymphocytic Choriomeningitis; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic / Q000235:genetics; D010195:Pancreatitis / Q000473:pathology / Q000517:prevention & control; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000494:pharmacology*; D051257:Proto-Oncogene Proteins c-maf; D013601:T-Lymphocytes / Q000166:cytology; D019076:Transgenes / Q000502:physiology
D004268:DNA-Binding Proteins; C495608:Maf protein, mouse; D011518:Proto-Oncogene Proteins; D051257:Proto-Oncogene Proteins c-maf