Manipulation of CD98 Resolves Type 1 Diabetes in Nonobese Diabetic Mice
Manipulation of CD98 Resolves Type 1 Diabetes in Nonobese Diabetic Mice
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DOI：
10.4049/jimmunol.1102586
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发表时间：
2012-03-01
影响因子：
4.4
通讯作者：
Yasutomo, Koji
中科院分区：
文献类型：
--
作者：
Lian, Gaojian;Arimochi, Hideki;Yasutomo, Koji
靶向自身抗原的CD 4（+）和CD 8（+）T细胞的相互作用是导致许多自身免疫性疾病（包括1型糖尿病（T1 D））进展的原因。了解调节T细胞活化的分子机制对于设计有效的自身免疫性疾病疗法至关重要。我们探测了一组具有T细胞调节活性的抗体，并鉴定了能够抑制T细胞增殖的CD 98 H链特异性mAb（CD 98 hc）。抗CD 98 hc mAb还在体外和体内抑制Ag特异性增殖以及CD 4（+）和CD 8（+）T细胞获得效应功能。注射抗CD 98 hc mAb完全防止NOD小鼠中环磷酰胺诱导的糖尿病的发作。用抗CD 98 hc治疗糖尿病NOD小鼠，可将糖尿病状态逆转至正常水平，与CD 4（+）T细胞增殖减少一致。此外，用CD 98 hc小干扰RNA治疗糖尿病NOD小鼠解决了T1 D。这些数据表明，靶向CD 98 hc的策略可能具有治疗T1 D和其他T细胞介导的自身免疫性疾病的临床应用。免疫学杂志，2012，188：2227-2234。
The interplay of CD4(+) and CD8(+) T cells targeting autoantigens is responsible for the progression of a number of autoimmune diseases, including type 1 diabetes mellitus (T1D). Understanding the molecular mechanisms that regulate T cell activation is crucial for designing effective therapies for autoimmune diseases. We probed a panel of Abs with T cell-modulating activity and identified a mAb specific for the H chain of CD98 (CD98hc) that was able to suppress T cell proliferation. The anti-CD98hc mAb also inhibited Ag-specific proliferation and the acquisition of effector function by CD4(+) and CD8(+) T cells in vitro and in vivo. Injection of the anti-CD98hc mAb completely prevented the onset of cyclophosphamide-induced diabetes in NOD mice. Treatment of diabetic NOD mice with anti-CD98hc reversed the diabetic state to normal levels, coincident with decreased proliferation of CD4(+) T cells. Furthermore, treatment of diabetic NOD mice with CD98hc small interfering RNA resolved T1D. These data indicate that strategies targeting CD98hc might have clinical application for treating T1D and other T cell-mediated autoimmune diseases. The Journal of Immunology, 2012, 188: 2227-2234.