The phenotype of autoreactive T cells in type 1 diabetes is described as Th1, Th17 and/or Th21, but is largely uncharacterized. We combined multi-parameter cytokine profiling and proliferation, and identified GM-CSF producing cells as a component of the response to beta cell autoantigens proinsulin and GAD65. Overall cytokine profiles of CD4⁺ T cell were not altered in type 1 diabetes. In contrast, patients with recent onset type 1 diabetes had increased frequencies of proinsulin-responsive CD4⁺ CD45RA⁻ T cells producing GM-CSF (p = 0.002), IFNγ (p = 0.004), IL-17A (p = 0.008), IL-21 (p = 0.011), and IL-22 (p = 0.007), and GAD65-responsive CD4⁺ CD45RA⁻ T cells producing IL-21 (p = 0.039). CD4⁺ T cells with a GM-CSF⁺IFNγ⁻IL-17A⁻IL-21⁻IL-22⁻ phenotype were increased in patients for responses to both proinsulin (p = 0.006) and GAD65 (p = 0.037). GM-CSF producing T cells are a novel phenotype in the repertoire of T helper cells in type 1 diabetes and consolidate a Th1/Th17 pro-inflammatory pathogenesis in the disease.

在1型糖尿病中，自身反应性T细胞的表型被描述为Th1，Th17和/或Th21，但大多没有特征。我们结合了多参数细胞因子分析和增殖，并确定产生GM-CSF的细胞是对β细胞自身抗原胰岛素原和GAD65应答的组成部分。在1型糖尿病中，CD4 ⁺ T细胞的总体细胞因子谱未改变。相比之下，近期发病的1型糖尿病患者中产生胰岛素原反应性CD4 ⁺  CD45RA ^- T细胞的频率增加，产生GM-CSF（p  = 0.002），IFNγ（p  = 0.004），IL-17A（p  = 0.008），IL -21（p  = 0.011）和IL-22（p = 0.007）和GAD65反应性CD4 ⁺  CD45RA ^- T细胞产生IL-21（p  = 0.039）。CD4 ⁺ T细胞与GM-CSF ⁺ IFNγ ^- IL-17A ^- IL-21 ^- IL-22 ^-表型在患者增加了两者胰岛素原（响应p  = 0.006）和GAD65（p  = 0.037）。产生GM-CSF的T细胞是1型糖尿病T辅助细胞库中的一个新表型，并巩固了该疾病的Th1 / Th17促炎性发病机制。