Erazo-Borrás L V, Álvarez-Álvarez J A, Perez-Romero C A, Orrego-Arango J C, Franco-Restrepo J L, Trujillo-Vargas C M
Grupo de Inmunodeficiencias Primarias, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
Scand J Immunol. 2017 Sep;86(3):171-178. doi: 10.1111/sji.12576.
Common variable immunodeficiency (CVID) is a syndrome with predominantly defective B cell function. However, abnormalities in the number and function of other lymphocyte subpopulations in peripheral blood (PB) have been described in most patients. We have analysed the distribution of iNKT cell subpopulations in the PB of CVID patients and the ability of these cells to provide in vitro cognate B cell help. The total of iNKT cells was reduced in the PB of CVID patients, especially CD4+, CD4-/CD8- and CCR5+/CXCR3+. These findings were associated with an enrichment of memory-like and a tendency towards a reduction in TNF-α-expressing effector iNKT cells in the peripheral blood mononuclear cells (PBMC) of CVID patients. Moreover, an accumulation of follicular helper iNKT cells in the PB of CVID patients was demonstrated. CVID αGalCer-pulsed iNKT cells are not able to induce autologous B cell proliferation although they do induce proliferation to healthy donor B cells. Interestingly, autologous and heterologous co-cultures did not differ in the amount of immunoglobulin secreted by B cells in vitro. Finally, reduced intracellular SAP expression in iNKT cells and other lymphocytes in the blood from CVID patients was observed. These results provide further insights into the immunological mechanisms underlying the iNKT cell defects and the potential targets to improve B cell help in CVID.
常见变异型免疫缺陷（CVID）是一种主要以B细胞功能缺陷为特征的综合征。然而，大多数患者外周血（PB）中其他淋巴细胞亚群的数量和功能存在异常。我们分析了CVID患者外周血中iNKT细胞亚群的分布以及这些细胞在体外提供同源B细胞辅助的能力。CVID患者外周血中iNKT细胞总数减少，尤其是CD4 +、CD4 - /CD8 - 和CCR5 + /CXCR3 + 细胞。这些发现与CVID患者外周血单个核细胞（PBMC）中记忆样细胞的富集以及表达肿瘤坏死因子-α的效应性iNKT细胞减少的趋势有关。此外，还证实了CVID患者外周血中滤泡辅助性iNKT细胞的积累。CVID患者经α半乳糖神经酰胺（αGalCer）刺激的iNKT细胞虽然能诱导健康供体B细胞增殖，但不能诱导自体B细胞增殖。有趣的是，自体和异体共培养中B细胞体外分泌的免疫球蛋白量没有差异。最后，观察到CVID患者血液中iNKT细胞和其他淋巴细胞内信号淋巴细胞激活分子（SAP）表达降低。这些结果为深入了解iNKT细胞缺陷的免疫机制以及改善CVID中B细胞辅助的潜在靶点提供了进一步的见解。
