Zeng Weihua, Maciejewski Jaroslaw P, Chen Guibin, Risitano Antonio M, Kirby Martha, Kajigaya Sachiko, Young Neal S
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Br J Haematol. 2002 Dec;119(3):803-9. doi: 10.1046/j.1365-2141.2002.03875.x.
T cell-mediated suppression of haematopoiesis is believed to play an important role in the pathophysiology of aplastic anaemia (AA) and in the pancytopenia of some myelodysplastic syndromes (MDS). Natural-killer T (NKT) cells belong to a unique lymphocyte subset that expresses an invariant T-cell receptor (TCR), consisting of Valpha24JalphaQ, and common NK cell surface markers. NKT cells have been hypothesized to play a role in immune regulation, and many human autoimmune conditions are associated with NKT cell deficiency. Here we investigate the role of NKT cells in AA and MDS patients. Flow cytometry demonstrated that NKT cells, unlike other T-lymphocyte subpopulations, were disproportionally decreased in AA and MDS marrow. When we compared variability within the CDR3 region of Valpha24 in CD4-CD8- T cells derived from AA and healthy individuals, the CDR3 size of Valpha24 cells showed a polyclonal distribution in AA patients, while in control subjects a typical oligoclonal or monoclonal pattern was found. Southern blot and sequence analysis of Valpha24 polymerase chain reaction products revealed that the NKT cell-specific JalphaQ region was predominant in control subjects, whereas it was not, or only very weakly, detected in AA and MDS patients. These results show that NKT cells are profoundly decreased in AA and MDS, and their deficiency may, as in other human autoimmune diseases, play a role in the local immune dysregulation in AA and MDS.
T细胞介导的造血抑制被认为在再生障碍性贫血（AA）的病理生理学以及某些骨髓增生异常综合征（MDS）的全血细胞减少中起重要作用。自然杀伤T（NKT）细胞属于独特的淋巴细胞亚群，表达由Valpha24JalphaQ组成的恒定T细胞受体（TCR）以及常见的NK细胞表面标志物。据推测，NKT细胞在免疫调节中起作用，许多人类自身免疫性疾病都与NKT细胞缺陷有关。在此，我们研究NKT细胞在AA和MDS患者中的作用。流式细胞术表明，与其他T淋巴细胞亚群不同，NKT细胞在AA和MDS骨髓中不成比例地减少。当我们比较来自AA患者和健康个体的CD4-CD8-T细胞中Valpha24的CDR3区域内的变异性时，Valpha24细胞的CDR3大小在AA患者中呈多克隆分布，而在对照受试者中则发现典型的寡克隆或单克隆模式。对Valpha24聚合酶链反应产物的Southern印迹和序列分析表明，NKT细胞特异性JalphaQ区域在对照受试者中占主导地位，而在AA和MDS患者中未检测到或仅非常微弱地检测到。这些结果表明，NKT细胞在AA和MDS中显著减少，并且与其他人类自身免疫性疾病一样，它们的缺陷可能在AA和MDS的局部免疫失调中起作用。
