Distinct overexpression of Fas ligand on T lymphocytes in aplastic anemia.
Increased expression of Fas by hematopoietic progenitors in aplastic anemia (AA) suggests that Fas/Fas ligand (FasL) system plays a key role in the formation of severe pancytopenia. To further confirm the above hypothesis, T cells from 8 patients with AA were systematically studied for their FasL's distribution pattern, releasing manner and proapoptotic activity, compared with normal resting T cells and artificially activated T cell blasts. The results demonstrated that AA T cells abnormally expressed low levels of membrane-bound FasL and contained high levels of intracellular FasL which could be triggered to release by high-dose phytohemagglutinin (PHA) pulse-stimulation. The supernatants from the PHA-stimulated AA T cells had apparent cytotoxicity against FasL-sensitive Jurkat cells, which could be significantly inhibited by monoclonal antibody against FasL in a dose-dependent manner, or nearly completely abrogated by ultracentrifugation. The above phenomena also appeared on artificially activated T cell blasts, but this was not the case on normal resting T cells. These results indicate that AA T cell is a type of "preactivated" T lymphocyte, characterized by overexpression of FasL, especially intracellular FasL which can be stimulated to release in bioactive exosomes-bound form. Taken together, our data provide further and direct evidence for the hypothesis that T cells might mediate the destruction of hematopoietic progenitor in AA through Fas/FasL system.
Li
Wenxin
W
Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China.
Fu
Jinxiang
J
Wang
Fengming
F
Yu
Gehua
G
Wang
Yong
Y
Zhang
Xueguang
X
D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000276:immunology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D010835:Phytohemagglutinins; D048069:Tumor Necrosis Factors