PMID- 32621335 OWN - NLM STAT- MEDLINE DCOM- 20210803 LR - 20210803 IS - 1098-2825 (Electronic) IS - 0887-8013 (Print) IS - 0887-8013 (Linking) VI - 34 IP - 10 DP - 2020 Oct TI - CTLA-4 and HLA-DQ are key molecules in the regulation of mDC-mediated cellular immunity by Tregs in severe aplastic anemia. PG - e23443 LID - 10.1002/jcla.23443 [doi] LID - e23443 AB - BACKGROUND: 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). METHODS: Flow cytometry was used to measure CD4(+) CD25(+) CD127(dim) 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. RESULTS: 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. CONCLUSIONS: 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. CI - (c) 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC. FAU - Liu, Bingnan AU - Liu B AUID- ORCID: 0000-0002-1938-4679 AD - Department of Hematology, Tianjin Medical University General Hospital, Tianjin, PR China. FAU - Shao, Yuanyuan AU - Shao Y AD - Department of Hematology, Tianjin Medical University General Hospital, Tianjin, PR China. FAU - Liang, Xiaowei AU - Liang X AD - Department of Hematology, Tianjin Medical University General Hospital, Tianjin, PR China. FAU - Lu, Dan AU - Lu D AD - Department of Hematology, Tianjin Medical University General Hospital, Tianjin, PR China. FAU - Yan, Li AU - Yan L AD - Department of Hematology, Tianjin Medical University General Hospital, Tianjin, PR China. FAU - Churov, Alexey AU - Churov A AUID- ORCID: 0000-0002-3920-7581 AD - Department of Hematology, Tianjin Medical University General Hospital, Tianjin, PR China. FAU - Fu, Rong AU - Fu R AD - Department of Hematology, Tianjin Medical University General Hospital, Tianjin, PR China. LA - eng GR - 16JCZDJC35300/Natural Science Foundation of Tianjin City/ GR - 17JCQNJC11500/Natural Science Foundation of Tianjin City/ GR - 18JCYBJC91700/Natural Science Foundation of Tianjin City/ GR - 18ZXDBSY00140/Natural Science Foundation of Tianjin City/ GR - 81700117/National Natural Science Foundation of China/ GR - 81700118/National Natural Science Foundation of China/ GR - 81770110/National Natural Science Foundation of China/ GR - 81770118/National Natural Science Foundation of China/ GR - 81800119/National Natural Science Foundation of China/ GR - 81800120/National Natural Science Foundation of China/ GR - 81870101/National Natural Science Foundation of China/ GR - 81900125/National Natural Science Foundation of China/ GR - 81970115/National Natural Science Foundation of China/ GR - 81970116/National Natural Science Foundation of China/ PT - Journal Article DEP - 20200703 PL - United States TA - J Clin Lab Anal JT - Journal of clinical laboratory analysis JID - 8801384 RN - 0 (CTLA-4 Antigen) RN - 0 (HLA-DQ Antigens) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Anemia, Aplastic/*immunology MH - CTLA-4 Antigen/*metabolism MH - Child MH - Dendritic Cells/*immunology MH - Female MH - HLA-DQ Antigens/*metabolism MH - Humans MH - *Immunity, Cellular MH - Killer Cells, Natural/immunology MH - Lymphocyte Count MH - Male MH - Middle Aged MH - T-Lymphocytes, Regulatory/*immunology MH - Young Adult PMC - PMC7595925 OTO - NOTNLM OT - cytotoxic T lymphocyte antigen 4 OT - human leukocyte antigen OT - regulatory T cells OT - severe aplastic anemia COIS- The authors declare no conflicts of interest. EDAT- 2020/07/06 06:00 MHDA- 2021/08/04 06:00 PMCR- 2020/07/03 CRDT- 2020/07/05 06:00 PHST- 2020/05/06 00:00 [received] PHST- 2020/06/01 00:00 [revised] PHST- 2020/06/03 00:00 [accepted] PHST- 2020/07/06 06:00 [pubmed] PHST- 2021/08/04 06:00 [medline] PHST- 2020/07/05 06:00 [entrez] PHST- 2020/07/03 00:00 [pmc-release] AID - JCLA23443 [pii] AID - 10.1002/jcla.23443 [doi] PST - ppublish SO - J Clin Lab Anal. 2020 Oct;34(10):e23443. doi: 10.1002/jcla.23443. Epub 2020 Jul 3.