Cell-mediated lysis of autologous platelets in chronic idiopathic thrombocytopenic purpura.
OBJECTIVE
Investigate the contribution and mechanism of cell-mediated cytotoxicity to the pathogenesis of idiopathic thrombocytopenic purpura (ITP).


METHODS
We observed the cytotoxic effect of cytotoxic T-lymphocyte (CTL) (CD8+) and natural killer cells (CD3- CD16+ CD56+) toward chronic ITP patient's autologous platelets, and investigated the expression of Fas ligand (FasL), tumor necrosis factor (TNF)-alpha and TNF-related apoptosis inducing ligand, as well as perforin and granzyme B mRNA in CD8+ cells using flow cytometry and reverse transcriptase-polymerase chain reaction.


RESULTS
We found that platelet lysis was seen only using purified CD8+ T cells as effector cells; expression of FasL and TNF-alpha in CD8+ T cells in ITP group was elevated. Moreover, the mRNA levels of granzyme B and perforin in CD8+ cells of ITP patients were increased.


CONCLUSIONS
Our findings suggest that CTLs are activated in chronic ITP and might be involved in the pathogenesis of this disorder. Apoptosis and perforin/granzyme-mediated cytotoxicity constitute an important pathway through which CTLs destruct autologous platelets. CTLs might be a reasonable target for a therapeutic strategy.
Hematology Oncology Center, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Feng
F
Zhang
Xiaoxia
X
Chu
Lin
L
Wang
Yuanyuan
Y
Zhu
Lizhen
L
Li
Daoxin
D
Ma
Jun
J
Peng
Ming
M
Hou
D000293:Adolescent; D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis; D001324:Autoantigens / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D053222:Fas Ligand Protein; D005260:Female; D005434:Flow Cytometry; D053804:Granzymes; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D012697:Serine Endopeptidases / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D048069:Tumor Necrosis Factors / Q000096:biosynthesis
D051017:Apoptosis Regulatory Proteins; D001324:Autoantigens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases