University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Clin Immunol. 2010 Nov;137(2):281-7. doi: 10.1016/j.clim.2010.07.013. Epub 2010 Aug 24.
To establish the relevance of targeting disease-associated T cells in anti-RNP-associated glomerulonephritis, mice developing nephritis following immunization with U1-70-kd small nuclear ribonucleoprotein (snRNP) were treated with a single dose of irradiated antigen-selected T cell vaccine. T cell receptor usage in nephritic kidneys revealed oligoclonal use of T Cell Receptor V Beta (TRBV) genes as previously found in spleens and lungs of immunized mice with pulmonary disease. The CDR3 regions from T cell isolates showed sequence homology to those in humans with anti-RNP autoimmunity. Following T cell vaccination, urinalysis returned to normal in 5/7 treated mice (71% response rate) whereas all mock-treated mice continued to have an active urinary sediment (Fisher's Exact p=0.02). An oligoclonal population of T cells homologous to those identified in humans with anti-RNP autoimmunity is implicated in disease pathogenesis, and T cell vaccination is associated with a high rate of clinical improvement in established nephritis.
为了确定针对抗 RNP 相关肾小球肾炎中疾病相关 T 细胞的相关性，用 U1-70-kd 小核核糖核蛋白（snRNP）免疫后发生肾炎的小鼠用单次剂量的照射抗原选择的 T 细胞疫苗进行治疗。在肾炎肾脏中检测到 T 细胞受体的使用情况，与以前在免疫小鼠的脾脏和肺部中发现的疾病相关，表现为 T 细胞受体 V Beta（TRBV）基因的寡克隆使用。T 细胞分离物的 CDR3 区域与具有抗 RNP 自身免疫的人类的序列同源。在 T 细胞接种疫苗后，5/7 例治疗小鼠（71%的反应率）的尿分析恢复正常，而所有假治疗小鼠继续出现活跃的尿沉渣（Fisher 确切概率 p=0.02）。与具有抗 RNP 自身免疫的人类中鉴定的同源的寡克隆 T 细胞群体与疾病发病机制有关，并且 T 细胞接种疫苗与已建立的肾炎的高临床改善率相关。
