1型糖尿病是一种由于T细胞诱导的胰岛β细胞的破坏凋亡引起的慢性自身免疫性疾病,。CD1d-restricted NKT淋巴细胞具有调节免疫的能力，这也包括调节自身免疫。既往的研究中，我们已经证实，携带多种T细胞抗原受体的CD1d-restricted II型 NKT 细胞能够阻止模拟人类糖尿病的NOD小鼠模型的1型糖尿病的进展。在本研究中,我们的研究结果显示：在接受转移性实验中，CD4(+)24αβII型NKT细胞,而不是CD4 / CD8双重阴性NKT细胞,就足以能够抑制致糖尿病的CD4(+)BDC2.5T细胞的免疫反应。同CD4 / CD8双重阴性NKT细胞相比，CD4(+)24αβNKT细胞表现出一种记忆表型，包括高表达ICOS,增加细胞因子产生和限制NK细胞标记的显示。可诱导协同刺激因子的抑制或者凋亡配体程序化路径引导了在胰腺淋巴系统调节机制中发生的破坏。我们的研究结果第一次从细胞和分子层面揭示了II型CD1d-restricted NKT细胞如何调节转化1型糖尿病的机制的。

CD4(+) type II NKT cells mediate ICOS and programmed death-1-dependent regulation of type 1 diabetes.

Type 1 diabetes (T1D) is a chronic autoimmune disease that results from T cell-mediated destruction of pancreatic β cells. CD1d-restricted NKT lymphocytes have the ability to regulate immunity, including autoimmunity. We previously demonstrated that CD1d-restricted type II NKT cells, which carry diverse TCRs, prevented T1D in the NOD mouse model for the human disease. In this study, we show that CD4(+) 24αβ type II NKT cells, but not CD4/CD8 double-negative NKT cells, were sufficient to downregulate diabetogenic CD4(+) BDC2.5 NOD T cells in adoptive transfer experiments. CD4(+) 24αβ NKT cells exhibited a memory phenotype including high ICOS expression, increased cytokine production, and limited display of NK cell markers, compared with double-negative 24αβ NKT cells. Blocking of ICOS or the programmed death-1/programmed death ligand 1 pathway was shown to abolish the regulation that occurred in the pancreas draining lymph nodes. To our knowledge, these results provide for the first time cellular and molecular information on how type II CD1d-restricted NKT cells regulate T1D.

链接：http://www.jimmunol.org/content/188/7/3138.long