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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 hypo-thesis,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 Tcell blasts.The results demonstrated that AA T cells abnormally expressed low levels of membrane-bound FasLand contained high levels of intracellular FasL which could be triggered to release by high-dose phyto-hemagglutinin(PHA)pulse-stimulation.The supernatants from the PHA-stimulated AA T cells had apparentcytotoxicity against FasL-sensitive Jurkat cells,which could be significantly inhibited by monocional antibodyagainst FasL in a dose-dependent manner,or nearly completely abrogated by ultracentrifugation.The abovephenomena also appeared on artificially activated T cell blasts,but this was not the case on normal resting Tcells.These results indicate that AA T cell is a type of“preactivated”T lymphocyte,characterized by over-expression of FasL,especially intracellular FasL which can be stimulated to release in bioavtive exosomes-bound form.Taken together,our data provide further and direct evidence for the hypothesis that T cells mightmediate the destruction of hematopietic progenitor in AA through Fas/FasL system.Cellular & MolecularImmunology.2004;1(2):142-147.
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 hypo-thesis, T cells from 8 patients with AA were systematically studied for their FasL’s distribution pattern, off manner and proapoptotic activity, compared with normal resting T cells and artificially activated Tcell blasts. the results demonstrated that AA T cells abnormally expressed low levels of membrane-bound FasLand contained high levels of intracellular FasL which could be triggered to release by high-dose phyto-hemagglutinin (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 antigen FasL in a dose -dependent manner, or almost completely abrogated by ultracentrifugation. above above alsoomena on artificially activated T c ell 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 over-expression of FasL, especially intracellular FasL which can be stimulated to release in bioavtive our data provide further and direct evidence for the hypothesis that T cells mightmediate the destruction of hematopietic progenitor in AA through Fas / FasL system. Cellular & Molecular Immunology. 2004; 1 (2): 142-147.