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Pathogenicity of T helper 2 T‐cell clones from T‐cell receptor transgenic non‐obese diabetic mice is determined by tumour necrosis factor‐α
Author(s) -
He Jing,
Haskins Kathryn
Publication year - 2008
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2007.02715.x
Subject(s) - t cell receptor , clone (java method) , biology , t cell , nod mice , cytotoxic t cell , adoptive cell transfer , tumor necrosis factor alpha , immunology , cd8 , antigen , autoimmune disease , immune system , in vitro , antibody , gene , genetics
Summary Autoimmune diabetes is predominated by a T helper 1 (Th1) response at the expense of an impaired Th2 response. Although T cells producing Th2 cytokines are generally thought to counter a Th1 response, there have been reports of Th2 T‐cell clones with pathogenic activity, including one previously reported by us in which the Th2 T‐cell clone was derived from a T‐cell receptor transgenic (TCR‐Tg) mouse bearing pathogenic TCR. In this study, our goal was to determine whether Th2 T‐cell clones derived from a TCR‐Tg in which the autoantigen was absent would be pathogenic and if so, to investigate possible mechanisms by which the Th2 T‐cell clone could promote disease. We found that a Th2 T‐cell clone derived from the 6·9 TCR‐Tg/non‐obese diabetic (NOD).C6 mouse in which 6.9 T cells do not encounter autoantigen, produced Th2 cytokines but not interferon‐γ. This Th2 T‐cell clone, like the previous one we had isolated from the 2.5 TCR‐Tg/NOD mouse, also turned out to be pathogenic. Intracellular staining revealed that these Th2 T‐cell clones produce low levels of tumour necrosis factor‐α (TNF‐α) in vitro , and after adoptive transfer, they migrate to the pancreas where they produce TNF‐α as well as Th2 cytokines (interleukin (IL)‐4, IL‐10). Induction of disease was prevented by administration of soluble TNF‐α receptor to recipient mice, suggesting that the diabetogenicity of these Th2 T‐cell clones is caused by their low level production of TNF‐α.