Fozza Claudio, Corda Giovanna, Virdis Patrizia, Contini Salvatore, Barraqueddu Francesca, Galleu Antonio, Isoni Antonella, Cossu Antonella, Dore Fausto, Careddu Maria G, Bonfigli Silvana, Giannico Barbara, Longinotti Maurizio
Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
Eur J Haematol. 2015 Apr;94(4):298-309. doi: 10.1111/ejh.12417. Epub 2014 Aug 22.
Although a number of studies suggest that different immune pathways may play a role in the pathogenesis of non-Hodgkin's lymphomas (NHL), the shape of the T-cell compartment has been only superficially explored in these patients. In our study, we analyzed the peripheral T-cell receptor (TCR) repertoire and the distribution of different T-cell subsets - including regulatory T cells (Treg) - in 30 patients with NHL, by combining flow cytometry and spectratyping. We first demonstrated by flow cytometry an increased frequency of expanded T-cell subpopulations expressing the same TCR beta variable (BV) subfamilies in CD8+ cells from NHL patients when compared with healthy controls, beside a higher frequency of Treg. Moreover, NHL patients were characterized by a higher percentage of BVs showing a skewed CDR3 profile both in CD4+ and CD8+ cells when analyzed by spectratyping. Our data suggest that the T-cell branch of the immune system of patients with B-cell NHL is deeply deranged, as witnessed by the increased degree of activation and skewing of their TCR repertoire along with the higher frequency of Treg.
尽管多项研究表明不同的免疫途径可能在非霍奇金淋巴瘤(NHL)的发病机制中起作用,但在这些患者中,T细胞区室的情况仅得到了初步探索。在我们的研究中,我们通过流式细胞术和光谱分型相结合的方法,分析了30例NHL患者外周血T细胞受体(TCR)库以及不同T细胞亚群(包括调节性T细胞(Treg))的分布。我们首先通过流式细胞术证明,与健康对照相比,NHL患者CD8+细胞中表达相同TCRβ可变(BV)亚家族的扩增T细胞亚群频率增加,同时Treg频率更高。此外,通过光谱分型分析,NHL患者的特征是在CD4+和CD8+细胞中,显示CDR3谱偏斜的BV百分比更高。我们的数据表明,B细胞NHL患者免疫系统的T细胞分支严重紊乱,这表现为其TCR库的激活程度和偏斜程度增加以及Treg频率更高。