To study the role of invariant Natural Killer T cell ( iNKT) cells in
autoimmune thyroiditis, we derived two iNKT cell lines from the spleens of NOD· H2(h4) mice, a strain that develops spontaneous
autoimmune thyroiditis exacerbated by excess dietary
iodine. The two lines were CD1d-restricted and expressed CD4(+), DX5(+), and the Vα4Jα281 gene segment, of the
T-cell receptor α locus. Upon stimulation with α-
galactosyl-ceramide (α-GalCer), both lines rapidly produced
IL-2,
IL-4, IFN-γ,
IL-10, and TNF-α. Strikingly, a similar
cytokine response was also induced by
thyroglobulin, one of the most abundant
protein in the thyroid gland and a major
autoantigen in human
autoimmune thyroiditis. Transfer of the iNKT cell lines to syngeneic hosts enhanced
autoimmune thyroiditis.
Intraperitoneal injections of α-GalCer in
iodine primed mice also induced
thyroid disease. This paper reports for the first time that iNKT cells respond to
thyroglobulin and enhance
autoimmune thyroiditis in
iodine fed NOD·H2(h4) mice.