CD8(+) T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia.
In addition to antiplatelet autoantibodies, CD8(+) cytotoxic T lymphocytes (CTLs) play an important role in the increased platelet destruction in immune thrombocytopenia (ITP). Recent studies have highlighted that platelet desialylation leads to platelet clearance via hepatocyte asialoglycoprotein receptors (ASGPRs). Whether CD8(+) T cells induce platelet desialylation in ITP remains unclear. Here, we investigated the cytotoxicity of CD8(+) T cells towards platelets and platelet desialylation in ITP. We found that the desialylation of fresh platelets was significantly higher in ITP patients with positive cytotoxicity of CD8(+) T cells than those without cytotoxicity and controls. In vitro, CD8(+) T cells from ITP patients with positive cytotoxicity induced significant platelet desialylation, neuraminidase-1 expression on the platelet surface, and platelet phagocytosis by hepatocytes. To study platelet survival and clearance in vivo, CD61 knockout mice were immunized and their CD8(+) splenocytes were used. Platelets co-cultured with these CD8(+) splenocytes demonstrated decreased survival in the circulation and increased phagocytosis in the liver. Both neuraminidase inhibitor and ASGPRs competitor significantly improved platelet survival and abrogated platelet clearance caused by CD8(+) splenocytes. These findings suggest that CD8(+) T cells induce platelet desialylation and platelet clearance in the liver in ITP, which may be a novel mechanism of ITP.
Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
Jihua
J
Qiu
Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
Xuena
X
Liu
School of Medicine, Zhejiang University, Hangzhou, China.
Xiaoqing
X
Li
Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
Xu
X
Zhang
Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
Panpan
P
Han
Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
Hai
H
Zhou
Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
Linlin
L
Shao
Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
Yu
Y
Hou
Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
Yanan
Y
Min
Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
Zhangyuan
Z
Kong
Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
Yawen
Y
Wang
Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
Yu
Y
Wei
Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
Xinguang
X
Liu
Canadian Blood Services and the Department of Laboratory Medicine and Pathobiology, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, Canada.
Heyu
H
Ni
Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.|Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China.
Jun
J
Peng
Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.|Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital, Shandong University, Jinan, China.|Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, China.
Ming
M
Hou
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000276:immunology; D001792:Blood Platelets / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000276:immunology; D006801:Humans; D008099:Liver / Q000276:immunology*; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009439:Neuraminidase / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology*; D055815:Young Adult
D037263:Asialoglycoprotein Receptor; D009439:Neuraminidase