| Summary: | 博士 === 國防醫學院 === 生命科學研究所 === 94 === 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 TH1 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 and expression of T-bet was also higher in CD4+hCD90+ cells than CD4+hCD90- cells in a TH1 polarized condition. Diabetic frequency was reduced in NOD.SCID recipients adoptivly transfered with hCD90-depleted splenocytes, confirming the pathogenic role of hCD90+ cells in autoimmune diabetes. To further investigate the effect of IL-12 on the development of TH1 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 TH1 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 TH1 development.
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