High programmed death 1 expression on T cells in aplastic anemia.
Programmed death 1 (PD-1) has been reported to be associated with aberrant regulation of T cells activation in aplastic anemia (AA). However, the connection between PD-1 expression status and AA needs to be further explored. The aim of this study is to investigate PD-1 expression status on T cells in AA patients and to explore the effect of PD-1 on apoptosis of T cells and BMHSCs. The concentration of platelet, lymphocyte and hemoglobin in peripheral blood of AA patients and healthy volunteers was detected by automatic blood-counter system. Mononuclear cells (MNCs) of peripheral blood and marrow were isolated from AA patients and healthy volunteers. PD-1 expression level on CD3+, CD4+, CD8+, CD4+CD25+FOXP3+ T cells and bone marrow hematopoietic stem cells (BMHSCs) and B7-H1 expression level on peripheral blood mononuclear cells (PBMCs) and BMHSCs were detected by flow cytometry (FCM). Cell apoptosis on T cells and BMHSCs was also detected by FCM. PD-1, B7-H1, Bax and Bcl-2 mRNA expression levels on T cells of peripheral blood were detected by real-time PCR. MNCs from healthy volunteers were treated with ammonium pyrrolidine dithiocarbamate (PDTC) to block the nuclear factor (NF)-кB pathway. Our results showed that in AA patients, T cells had high levels of PD-1 expression and apoptosis rate. In BMHSCs, apoptosis rate was also higher than healthy volunteers. The expression of PD-1 on T cells was correlated with lymphocyte count and hemoglobin level. PD-1 was highly expressed on CD4+CD25+FOXP3+ T cells of AA patients and PD-1 expression was negatively correlated with the percentage of CD4+CD25+FOXP3+ T cells in AA patients. B7-H1, the ligand of PD-1, was also highly expressed on T cells, B cells, PBMCs and BMHSCs. When the NF-κB pathway was blocked by PDTC, the apoptosis of T cells and BMHSCs was reduced in a dose-dependent manner and PD-1 expression was also decreased in a dose-dependent manner. In conclusion, PD-1 was up-regulated in T cells in AA patients compared with healthy volunteers. The NF-κB pathway participated in the process of apoptosis of CD4+CD25+FOXP3+ T cells and BMHSCs induced by PD-1 in AA patients.
Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China. Electronic address: zhaowred@163.com.
Wanhong
W
Zhao
Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Yilin
Y
Zhang
Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Pengyu
P
Zhang
Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University, Health Science Center, Xi'an 710061, China.
Juan
J
Yang
Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Longjin
L
Zhang
Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Aili
A
He
Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
Wanggang
W
Zhang
Division of Hematology, Department of Medicine, Nippon Medical School, Tokyo, Japan.
Tamura
T
Hideto
D000741:Anemia, Aplastic / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology*; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers; D001772:Blood Cell Count; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
D060890:B7-H1 Antigen; D015415:Biomarkers; C423236:CD274 protein, human; D016328:NF-kappa B; D061026:Programmed Cell Death 1 Receptor
Aplastic anemia; NF-κB; Programmed death 1; T cells; apoptosis