Immunopathogenic role of TH1 cells in autoimmune diabetes: evidence from a T1 and T2 doubly transgenic non-obese diabetic mouse model - PubMed (original) (raw)

Immunopathogenic role of TH1 cells in autoimmune diabetes: evidence from a T1 and T2 doubly transgenic non-obese diabetic mouse model

Jung-Tung Hung et al. J Autoimmun. 2005 Nov.

Abstract

To improve the feasibility of in vivo monitoring of autoreactive T cells in the diabetogenic process, we generated T1 and T2 doubly transgenic non-obese diabetic (NOD) mice in which transgenic human CD90 (hCD90) is simultaneously expressed on IFN-gamma-producing cells or murine CD90.1 (mCD90.1) is expressed on IL-4-producing cells. These transgenic NOD mice develop diabetes with the same kinetics and incidence as wild type NOD mice, permitting the physiological characterization of CD4(+)hCD90(+) cells, which represent T(H)1 cells in lymphoid organs and at the site of insulitis. CD4(+)hCD90(+) cells had a higher capacity to secret IFN-gamma than CD4(+)hCD90(-) cells in an autoantigen-specific manner. Transgenic mice treated with GAD65 plasmid were protected from autoimmune diabetes, and had a lower number of CD4(+)hCD90(+) cells, confirming the pathogenic role of CD4(+)hCD90(+) cells in autoimmune diabetes. To further investigate the effect of IL-12 on the development of T(H)1 cells in autoimmune diabetes, we crossed these doubly transgenic mice to IL-12p35-deficient NOD mice. Despite severe disturbance of diabetes in p35(-/-) mice, the frequency of T(H)1 cells in these mice was slightly lower than in wild type mice. These data support the pathological role of IL-12 in autoimmune diabetes and suggest the existence an IL-12-independent pathway of T(H)1 development.

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