CTLA-4 and HLA-DQ are key molecules in the regulation of mDC-mediated cellular immunity by Tregs in severe aplastic anemia.
CTLA-4 and HLA-DQ are key molecules in the regulation of mDC-mediated cellular immunity by Tregs in severe aplastic anemia.
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CTLA-4和HLA-DQ是严重再生障碍性贫血中Tregs调节mDC介导的细胞免疫的关键分子
DOI：
10.1002/jcla.23443
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发表时间：
2020-10
影响因子：
2.7
通讯作者：
Fu R
中科院分区：
文献类型：
--
作者：
Liu B;Shao Y;Liang X;Lu D;Yan L;Churov A;Fu R
调节性T细胞（Tregs）抑制cd4 +、CD8+T细胞的活化以及抗原-递呈细胞的抗原-递呈过程，可能在获得性严重再生障碍性贫血（SAA）中发挥重要作用。流式细胞术检测CD4+CD25+CD127dim treg，细胞毒性T淋巴细胞抗原4 （CTLA‐4）在treg上的表达，以及人白细胞抗原（HLA）‐DQ在骨髓树突状细胞（mDCs）上的表达。分析CTLA‐4和HLA‐DQ与免疫状态和临床指标的相关性，以及免疫抑制治疗（IST）后这些指标的变化。SAA患者treg数量和CTLA - 4表达较低，经IST治疗后恢复；HLA - DQ在mDCs中的表达较高，但经IST治疗后降低。treg细胞上CTLA‐4的表达与mDCs细胞上HLA‐DQ的表达呈负相关。Tregs上的CTLA‐4与Tregs数量、NK细胞数量、CD4+T/CD8+T比值呈显著负相关，而mDCs上的HLA‐DQ呈显著负相关。CTLA‐4与骨髓中粒细胞和红细胞百分比、PB中白细胞计数、PB中绝对中性粒细胞计数和PB中网织红细胞百分比呈正相关，而HLA‐DQ与之呈负相关。CTLA‐4/HLA‐DQ可能是SAA患者中Tregs对mDCs调节的关键。本研究结果对进一步探讨SAA患者的免疫发病机制具有一定的指导意义。研究Treg和CTLA - 4活性调控因子对SAA治疗靶点研究和疾病监测具有重要意义。CTLA‐4和HLA‐DQ通过Tregs和mDC调节SAA的细胞免疫。A， CD4+CD125+CD127dim/PBL在SAA， RSAA和HC组。B， CTLA‐4+Treg/Treg在SAA， RSAA和HC组。C， HLA - DQ+mDC/mDC在SAA， RSAA和HC组。D， SAA患者treg细胞上CTLA‐4的表达与mDCs细胞上HLA‐DQ的表达呈负相关。*** p < 0.001, ** p < 0.01, * p < 0.05。HC，健康对照（n = 24）；RSAA，恢复期重度再生障碍性贫血（n = 23）；SAA，严重再生障碍性贫血（n = 21）。
Regulatory T cells (Tregs) inhibit the activation of cluster of differentiation (CD) 4+, CD8+T cells and the antigen‐presenting process of antigen‐presenting cells, and may play an important role in acquired severe aplastic anemia (SAA). Flow cytometry was used to measure CD4+CD25+CD127dim Tregs, cytotoxic T lymphocyte antigen 4 (CTLA‐4) expression on Tregs, and human leukocyte antigen (HLA)‐DQ expression on myeloid dendritic cells (mDCs). The correlations of CTLA‐4 and HLA‐DQ with immune status and clinical indicators and the changes in these indicators after immunosuppressive therapy (IST) were analyzed. In SAA patients, the number of Tregs and their CTLA‐4 expression were low but recovered after IST; the HLA‐DQ expression on mDCs was high but decreased after IST. The CTLA‐4 expression on Tregs and the HLA‐DQ expression on mDCs showed a negative correlation. The CTLA‐4 on Tregs was positively but HLA‐DQ on mDCs negatively correlated with the number of Tregs, natural killer (NK) cell number, and CD4+T/CD8+T ratio. CTLA‐4 was positively but HLA‐DQ negatively correlated with the percentage of granulocytoid and erythroid cells in bone marrow, white blood cell count in PB, absolute neutrophil count in PB, and the percentage of reticulocytes in PB. CTLA‐4/HLA‐DQ may be key in the regulation of Tregs on mDCs in SAA patients. Our findings should be helpful for further investigation of the mechanism of immune pathogenesis in SAA patients. Studies on the regulators of Treg and CTLA‐4 activity will be valuable for SAA therapeutic target research and disease monitoring. CTLA‐4 and HLA‐DQ regulate cellular immunity by Tregs and mDC in SAA. A, CD4+CD125+CD127dim/PBL in the SAA, RSAA, and HC groups. B, CTLA‐4+Treg/Treg in the SAA, RSAA, and HC groups. C, HLA‐DQ+mDC/mDC in the SAA, RSAA, and HC groups. D, Negative correlation between the CTLA‐4 expression on Tregs and the HLA‐DQ expression on mDCs in SAA patients. ***P < .001, **P < .01, *P < .05. HC, healthy control (n = 24); RSAA, recovering severe aplastic anemia (n = 23); SAA, severe aplastic anemia (n = 21).
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影响因子：
--
作者：
Golding, Amit;Hasni, Sarfaraz;Illei, Gabor;Shevach, Ethan M.
通讯作者：
Shevach, Ethan M.
影响因子：
12.8
作者：
Walker LS
通讯作者：
Walker LS
DOI：
10.4049/jimmunol.1601135
发表时间：
2016-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Adams AB;Ford ML;Larsen CP
通讯作者：
Larsen CP
CD127表达与FOXP3和人类CD4+ T Reg细胞的抑制功能成反比。
DOI：
10.1084/jem.20060772
发表时间：
2006-07-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.2
作者：
Rothstein DM;Camirand G
通讯作者：
Camirand G