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Apoptosis of Autoreactive CD8 Lymphocytes as a Potential Mechanism for the Abrogation of Type 1 Diabetes by Islet‐Specific TNF‐α Expression at a Time When the Autoimmune Process Is Already Ongoing
Author(s) -
CHRISTEN URS,
HERRATH MATTHIAS G.
Publication year - 2002
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2002.tb02962.x
Subject(s) - lymphocytic choriomeningitis , immunology , tumor necrosis factor alpha , type 1 diabetes , beta cell , cd8 , beta (programming language) , reversion , apoptosis , biology , medicine , islet , endocrinology , diabetes mellitus , immune system , gene , genetics , programming language , computer science , phenotype
A bstract : The role of TNF‐α in type 1 diabetes pathogenesis is controversial. Using double transgenic mice expressing (i) the glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV) as an islet self‐antigen and (ii) TNF‐α under control of a tetracycline‐regulated promotor system (tTA) in the pancreatic β cells, we could previously demonstrate a differential effect of TNF‐α on the incidence of type 1 diabetes. Most interestingly, late expression of TNF‐α resulted in a reversion of mice that were already diabetic to a nondiabetic state. Here we provide a model of how experienced autoaggressive CD8 lymphocytes are dying by apoptosis as a result of β cell‐specific TNF‐α expression at a time when the autoimmune process is already ongoing.