Abstract
Objectives:
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.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adolescent
-
Adult
-
Apoptosis Regulatory Proteins / biosynthesis
-
Autoantigens / immunology*
-
Blood Platelets / immunology*
-
CD8-Positive T-Lymphocytes / immunology
-
Chronic Disease
-
Cytotoxicity, Immunologic / immunology*
-
Fas Ligand Protein
-
Female
-
Flow Cytometry
-
Granzymes
-
Humans
-
Killer Cells, Natural / immunology
-
Male
-
Membrane Glycoproteins / biosynthesis
-
Membrane Glycoproteins / genetics
-
Membrane Glycoproteins / immunology
-
Middle Aged
-
Perforin
-
Pore Forming Cytotoxic Proteins
-
Purpura, Thrombocytopenic, Idiopathic / blood
-
Purpura, Thrombocytopenic, Idiopathic / immunology*
-
RNA, Messenger / genetics
-
RNA, Messenger / immunology
-
Serine Endopeptidases / genetics
-
Serine Endopeptidases / immunology
-
T-Lymphocytes, Cytotoxic / immunology
-
TNF-Related Apoptosis-Inducing Ligand
-
Tumor Necrosis Factor-alpha / biosynthesis
-
Tumor Necrosis Factors / biosynthesis
Substances
-
Apoptosis Regulatory Proteins
-
Autoantigens
-
FASLG protein, human
-
Fas Ligand Protein
-
Membrane Glycoproteins
-
Pore Forming Cytotoxic Proteins
-
RNA, Messenger
-
TNF-Related Apoptosis-Inducing Ligand
-
TNFSF10 protein, human
-
Tumor Necrosis Factor-alpha
-
Tumor Necrosis Factors
-
Perforin
-
GZMB protein, human
-
Granzymes
-
Serine Endopeptidases