Immunopathogenic role of T_H1 cells in autoimmune diabetes: Evidence from a T1 and T2 doubly transgenic non-obese diabetic mouse model

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• 作者：Jung-Tung Hung ; Jen-Hsiang Liao ; Yu-Chung Lin ; Hsiu-Ying Chang ; Shu-Fen Wu ; Tsung-Hsien Chang ; John T. Kung ; Shie-Liang Hsieh ; Hugh McDevitt and Huey-Kang Sytwu
• 关键词：NOD ; T_H1/T_H2 ; GAD65
• 刊名：Journal of Autoimmunity
• 出版年：2005
• 出版时间：November 2005
• 年：2005
• 卷：25
• 期：3
• 页码：181-192
• 全文大小：774 K

文摘

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-γ-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_H1 cells in lymphoid organs and at the site of insulitis. CD4⁺hCD90⁺ cells had a higher capacity to secret IFN-γ 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_H1 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_H1 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_H1 development.