La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA; University of California San Diego, San Diego, CA, USA.
J Autoimmun. 2014 May;50:77-82. doi: 10.1016/j.jaut.2013.12.003. Epub 2013 Dec 30.
Previous cross-sectional analyses demonstrated that CD8(+) and CD4(+) T-cell reactivity to islet-specific antigens was more prevalent in T1D subjects than in healthy donors (HD). Here, we examined T1D-associated epitope-specific CD4(+) T-cell cytokine production and autoreactive CD8(+) T-cell frequency on a monthly basis for one year in 10 HD, 33 subjects with T1D, and 15 subjects with T2D. Autoreactive CD4(+) T-cells from both T1D and T2D subjects produced more IFN-γ when stimulated than cells from HD. In contrast, higher frequencies of islet antigen-specific CD8(+) T-cells were detected only in T1D. These observations support the hypothesis that general beta-cell stress drives autoreactive CD4(+) T-cell activity while islet over-expression of MHC class I commonly seen in T1D mediates amplification of CD8(+) T-cells and more rapid beta-cell loss. In conclusion, CD4(+) T-cell autoreactivity appears to be present in both T1D and T2D while autoreactive CD8(+) T-cells are unique to T1D. Thus, autoreactive CD8(+) cells may serve as a more T1D-specific biomarker.
先前的横断面分析表明，1 型糖尿病（T1D）患者的胰岛特异性抗原 CD8(+)和 CD4(+)T 细胞反应比健康供体（HD）更为常见。在这里，我们在一年内每月检查了 10 名 HD、33 名 T1D 患者和 15 名 T2D 患者的 T1D 相关表位特异性 CD4(+)T 细胞细胞因子产生和自身反应性 CD8(+)T 细胞频率。与 HD 相比，T1D 和 T2D 患者的自身反应性 CD4(+)T 细胞在受到刺激时产生更多的 IFN-γ。相比之下，仅在 T1D 中检测到胰岛抗原特异性 CD8(+)T 细胞的频率更高。这些观察结果支持这样一种假设，即一般的β细胞应激会驱动自身反应性 CD4(+)T 细胞的活性，而 T1D 中常见的 MHC 类 I 的胰岛过表达会放大 CD8(+)T 细胞并导致更快的β细胞丢失。总之，CD4(+)T 细胞自身反应性似乎存在于 T1D 和 T2D 中，而自身反应性 CD8(+)T 细胞则是 T1D 所特有的。因此，自身反应性 CD8(+)细胞可能是更具 T1D 特异性的生物标志物。
