Melo Karina M, Carvalho Karina I, Bruno Fernanda R, Ndhlovu Lishomwa C, Ballan Wassim M, Nixon Douglas F, Kallas Esper G, Costa-Carvalho Beatriz T
Federal University of São Paulo, São Paulo, Brazil.
PLoS One. 2009 Jul 29;4(7):e6269. doi: 10.1371/journal.pone.0006269.
Common variable immunodeficiency disorder (CVID) is a heterogeneous syndrome, characterized by deficient antibody production and recurrent bacterial infections in addition abnormalities in T cells. CD4(+)CD25(high) regulatory T cells (Treg) are essential modulators of immune responses, including down-modulation of immune response to pathogens, allergens, cancer cells and self-antigens.
In this study we set out to investigate the frequency of Treg cells in CVID patients and correlate with their immune activation status.
Sixteen patients (6 males and 10 females) with CVID who had been treated with regular intravenous immunoglobulin and 14 controls were enrolled. Quantitative analyses of peripheral blood mononuclear cells (PBMC) were performed by multiparametric flow cytometry using the following cell markers: CD38, HLA-DR, CCR5 (immune activation); CD4, CD25, FOXP3, CD127, and OX40 (Treg cells); Ki-67 and IFN-gamma (intracellular cytokine).
A significantly lower proportion of CD4(+)CD25(high)FOXP3 T cells was observed in CVID patients compared with healthy controls (P<0.05). In addition to a higher proportion of CD8(+) T cells from CVID patients expressing the activation markers, CD38(+) and HLA-DR(+) (P<0.05), we observed no significant correlation between Tregs and immune activation.
Our results demonstrate that a reduction in Treg cells could have impaired immune function in CVID patients.
常见变异型免疫缺陷病(CVID)是一种异质性综合征,其特征是抗体产生不足、反复细菌感染以及T细胞异常。CD4(+)CD25(高表达)调节性T细胞(Treg)是免疫反应的重要调节因子,包括对病原体、过敏原、癌细胞和自身抗原的免疫反应下调。
在本研究中,我们着手调查CVID患者中Treg细胞的频率,并将其与免疫激活状态相关联。
招募了16例接受常规静脉注射免疫球蛋白治疗的CVID患者(6例男性和10例女性)以及14名对照。使用以下细胞标志物通过多参数流式细胞术对外周血单个核细胞(PBMC)进行定量分析:CD38、HLA-DR、CCR5(免疫激活);CD4、CD25、FOXP3、CD127和OX40(Treg细胞);Ki-67和IFN-γ(细胞内细胞因子)。
与健康对照相比,CVID患者中CD4(+)CD25(高表达)FOXP3 T细胞的比例显著降低(P<0.05)。除了CVID患者中表达激活标志物CD38(+)和HLA-DR(+)的CD8(+) T细胞比例更高(P<0.05)外,我们未观察到Tregs与免疫激活之间存在显著相关性。
我们的结果表明,Treg细胞减少可能会损害CVID患者的免疫功能。