监测 1 型糖尿病患者用抗 CD3 单克隆抗体治疗后抗原特异性 CD8 T 细胞的情况。
Monitoring of antigen-specific CD8 T cells in patients with type 1 diabetes treated with antiCD3 monoclonal antibodies.
机构信息
Department of Immunobiology, Yale University, 10 Amistad Street, 131D, New Haven, CT 06520, USA.
出版信息
Clin Immunol. 2010 Feb;134(2):121-9. doi: 10.1016/j.clim.2009.09.005.
The way in which anti-CD3 monoclonal antibodies (mAbs) modify human immune responses in type 1 diabetes (T1DM) is not known. We prepared a panel of Class I HLA-A2.1 tetramers with peptides from diabetes-associated antigens and studied the frequency and phenotype of the cells in patients with T1DM and blood donors and in patients treated with anti-CD3 mAb (Teplizumab). More patients with T1DM showed positive staining for at least 1 tetramer using frozen and fresh samples (p<0.05). Three months following treatment with anti-CD3 mAb, the proportion of GAD65- and InsB-peptide reactive CD8+ T cells increased (p<0.05). The phenotype of these cells was modulated from naïve to effector memoryRA+. We concludethat Class I MHC tetramers can identify antigen specific CD8+ T cells in patients with T1DM. The frequency of certain specificities increases after treatment with anti-CD3 mAb. Their modulated phenotype may have functional consequences for their pathogenicity.
抗 CD3 单克隆抗体（mAbs）在 1 型糖尿病（T1DM）中改变人类免疫反应的方式尚不清楚。我们制备了一组包含来自糖尿病相关抗原的肽的 I 类 HLA-A2.1 四聚体，并研究了 T1DM 患者、献血者和接受抗 CD3 mAb（Teplizumab）治疗的患者中这些细胞的频率和表型。使用冷冻和新鲜样本，更多的 T1DM 患者至少对 1 种四聚体呈阳性染色（p<0.05）。抗 CD3 mAb 治疗 3 个月后，GAD65 和 InsB 肽反应性 CD8+T 细胞的比例增加（p<0.05）。这些细胞的表型从幼稚到效应记忆 RA+被调节。我们的结论是，I 类 MHC 四聚体可以鉴定 T1DM 患者中的抗原特异性 CD8+T 细胞。治疗后某些特异性的频率增加。它们调节的表型可能对其致病性有功能后果。
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