期刊
JOURNAL OF IMMUNOLOGY
卷 166, 期 12, 页码 7023-7032出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.166.12.7023
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- NIAID NIH HHS [R01AI4451] Funding Source: Medline
- NIDDK NIH HHS [R29 DK51091] Funding Source: Medline
We report here that islet-specific expression of TNF-alpha can play a dual role in autoimmune diabetes, depending on its precise timing in relation to the ongoing autoimmune process. In a transgenic model (rat insulin promoter-lymphocytic choriomeningitis virus) of virally induced diabetes, TNF-alpha enhanced disease incidence when induced through an islet-specific tetracycline-dependent promoter system early during pathogenesis. Blockade of TNF-a during this phase prevented diabetes completely, suggesting its pathogenetic importance early in disease development. In contrast, TNF-a expression abrogated the autoimmune process when induced late, which was associated with a reduction of autoreactive CD8 lymphocytes in islets and their lytic activities. Thus, the fine-tuned kinetics of an autoreactive process undergo distinct stages that respond in a differential way to the presence of TNF-a. This observation has importance for understanding the complex role of inflammatory cytokines in autoimmunity.
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