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 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 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 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 monocional 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 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 might mediate the destruction of hematopietic progenitor in AA through Fas/FasL system.Cellular & Molecular Immunology.2004;1(2):142-147.