Distinct Overexpression of Fas Ligand on T Lymphocytes in Aplastic Anemia

摘要

＜正＞ 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.