Interleukin 12 administration induces T helper type 1 cells and accelerates autoimmune diabetes in NOD mice.
T cells play a major role in the development of insulin-dependent diabetes mellitus (IDDM) in nonobese diabetic (NOD) mice. Administration of interleukin 12 (IL-12), a key cytokine which guides the development of T helper type 1 (Th1) CD4+ T cells, induces rapid onset of IDDM in NOD, but not in BALB/c mice. Histologically, IL-12 administration induces massive infiltration of lymphoid cells, mostly T cells, in the pancreatic islets of NOD mice. CD4+ pancreas-infiltrating T cells, after activation by insolubilized anti T cell receptor antibody, secrete high levels of interferon gamma and low levels of IL-4. Therefore, IL-12 administration accelerates IDDM development in genetically susceptible NOD mice, and this correlates with increased Th1 cytokine production by islet-infiltrating cells. These results hold implications for the pathogenesis, and possibly for the therapy of IDDM and of other Th1 cell-mediated autoimmune diseases.
Roche Milano Ricerche, Italy.
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Trembleau
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Penna
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Bosi
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Mortara
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Gately
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Adorini
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D016466:CHO Cells; D006224:Cricetinae; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000008:administration & dosage / Q000494:pharmacology*; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma