Distinct overexpression of Fas ligand on T lymphocytes in aplastic anemia

Abstract

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.