Zeng L J, Liu C Y, Ding S X, Zhang T, Shao Z H, Fu R
Department of Hematology, General Hospital, Tianjin Medical University, Tianjin 300052, China.
Zhonghua Xue Ye Xue Za Zhi. 2018 Nov 14;39(11):927-931. doi: 10.3760/cma.j.issn.0253-2727.2018.11.011.
To explore the expression of SLAMF6 on CD8(+) T cells in patients with severe aplastic anemia (SAA) and its correlation with disease immune status. By flow cytometry (FCM), SLAMF6 expression level in peripheral blood CD8(+) T cells was detected in 21 patients with SAA and 15 normal controls respectively from February 2017 to April 2018. The correlation between SLAMF6 expression level and hematopoietic functions, including HGB, PLT, the neutrophil granulocyte and reticulocyte absolute value in peripheral blood, hyperplasia degree (percentage of granulocytes, erythrocytes, lymphocytes and megakaryocytes in bone marrow) and perforin, granzyme B, IFN-γ expression level in CD8(+) T cells were evaluated. To further confirm the effect of SLAMF6 on CD8(+) T cells, anti-SLAMF6 Ab was used to block SLAMF6 pathway (IgG as control), and FCM was used to detect the perforin, granzyme B, and IFN-γ production of CD8(+) T cells. The expression of SLAMF6 on CD8(+) T cells in untreated SAA patients[(56.29±12.97)%]was significantly lower than that of normal controls[(80.96±7.36)%](=-7.672, <0.001). The expression of SLAMF6 on CD8(+) T cells in SAA patients were positively correlated with the HGB, PLT, the neutrophil granulocyte and reticulocyte absolute value in peripheral blood, percentage of granulocytes, erythrocytes in bone marrow (all <0.05), but they were negatively correlated with the percentage of lymphocytes in bone marrow, and the expression of perforin, granzyme B, and IFN-γ of CD8(+) T cells (all <0.05). After blocking SLAMF6 pathway by anti-SLAMF6 Ab, the expression levels of perforin, granzyme B and IFN-γ in SAA patients were significantly higher than those in the untreated group, and the differences were statistically significant (all <0.05). SLAMF6 is significantly down-regulated on CD8(+) T cells in SAA patients, which may act as a negative immunoregulatory molecule participating in the mechanism of SAA by affecting the functional molecules secretion on CD8(+) T cells.
探讨重型再生障碍性贫血（SAA）患者CD8(+) T细胞上信号淋巴细胞激活分子家族成员6（SLAMF6）的表达及其与疾病免疫状态的相关性。采用流式细胞术（FCM），分别检测2017年2月至2018年4月期间21例SAA患者和15名正常对照外周血CD8(+) T细胞中SLAMF6的表达水平。评估SLAMF6表达水平与造血功能的相关性，包括外周血血红蛋白（HGB）、血小板（PLT）、中性粒细胞和网织红细胞绝对值，骨髓增生程度（骨髓中粒细胞、红细胞、淋巴细胞和巨核细胞的百分比）以及CD8(+) T细胞中穿孔素、颗粒酶B、干扰素-γ（IFN-γ）的表达水平。为进一步证实SLAMF6对CD8(+) T细胞的作用，使用抗SLAMF6抗体阻断SLAMF6通路（以IgG作为对照），并采用FCM检测CD8(+) T细胞中穿孔素、颗粒酶B和IFN-γ的产生。未经治疗的SAA患者CD8(+) T细胞上SLAMF6的表达水平[（56.29±12.97）%]显著低于正常对照[（80.96±7.36）%]（=-7.672，<0.001）。SAA患者CD8(+) T细胞上SLAMF6的表达与外周血HGB、PLT、中性粒细胞和网织红细胞绝对值、骨髓中粒细胞和红细胞百分比均呈正相关（均<0.05），但与骨髓中淋巴细胞百分比以及CD8(+) T细胞中穿孔素、颗粒酶B和IFN-γ的表达呈负相关（均<0.05）。用抗SLAMF6抗体阻断SLAMF6通路后，SAA患者穿孔素、颗粒酶B和IFN-γ的表达水平显著高于未治疗组，差异具有统计学意义（均<0.05）。SAA患者CD8(+) T细胞上SLAMF6显著下调，可能作为负性免疫调节分子，通过影响CD8(+) T细胞上功能分子的分泌参与SAA的发病机制。
