Beta cell death and protection.
Type 1 diabetes is an immune-mediated disease critically dependent upon the interaction between antigen-presenting cells and T cells. Clearly, both CD4+ and CD8+ T cells are required, but activated CD4+ T cells are both necessary and sufficient in causing disease. The mechanism of the Th1/Th2 immunoregulatory imbalance is unclear and needs to be further investigated. CD8+ T cells are not commonly sufficient in causing disease, but CD8 T cells are necessary in initiation (<14 weeks in the NOD mouse), but not in the later (>14 weeks) effector phase of the disease. It is still unclear whether the CD8+ T cell exerts its function as a classical effector cell or mainly as an immunomodulatory cell acting in synergy with the CD4+ T cell. The relative role of T cell effector mechanisms such as Fas/FasL, perforin/granzyme, and the TRAIL systems is unclear. Proinflammatory cytokines, reactive oxygen species, and other immune mediators seem to be involved in beta cell destruction, but much is to be learned about signaling, molecular mechanisms, and in vivo importance.
Mandrup-Poulsen
Thomas
T
Steno Diabetes Center, Gentofte, Denmark. tmpo@steno.dk
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D016923:Cell Death; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology; D053222:Fas Ligand Protein; D053804:Granzymes; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D016688:Mice, Inbred NOD; D018384:Oxidative Stress; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D019014:fas Receptor / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases; C509212:GZMA protein, human