Beneficial autoimmunity in Type 1 diabetes mellitus.
The trigger that leads to the pathogenesis of type 1 diabetes is currently unknown. It is well established that the pathophysiology of the disease is biphasic. In the first stage, leukocytes infiltrate the pancreatic islets in a response that does not cause damage. In the second phase, which occurs only in diabetes-prone individuals and strains, autoreactive T cells acquire aggressive potential and destroy the majority of the pancreatic islets. Rodents and humans exhibit a physiological ripple of apoptotic beta-cell death shortly after birth, which induces an adaptive autoimmune response towards islet-antigens, both in diabetes-prone non-obese diabetic (NOD) mice and in mice that do not develop diabetes. Here, we propose that the early T cell-mediated autoimmune response towards islet-antigens is physiological, purposeful and beneficial.
Hauben
Ehud
E
San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Via Olgettina 58, Milan 20132, Italy. hauben@ehud@hsr.it
Roncarolo
Maria Grazia
MG
Nevo
Uri
U
Schwartz
Michal
M
D000818:Animals; D017209:Apoptosis; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D006706:Homeostasis; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology