Fas-FasL-mediated CD4+ T-cell apoptosis following stem cell transplantation.

We report the preferential expression of Fas on CD4 + T cells and Fas ligand (FasL) on monocytes and their potential role in the selective loss of CD4 + T cells in breast cancer patients undergoing high-dose chemotherapy and peripheral blood stem cell transplantation (PSCT). A high frequency of apoptotic CD4 + T cells (28–51%) is observed during the first 100 days after PSCT concomitant with a significant increase in monocyte frequency and FasL expression (11.6–23%) on monocytes. The preferential expression of Fas on CD4 + T cells (73–92%) in the peripheral blood (PB) of these patients is associated with a significantly higher frequency of CD4 + T-cell apoptosis compared with CD8 + T cells (28–47%) and CD4 + T cells (46 ± 5.7%) in normal PB. These data suggest that “primed” Fas + CD4 + lymphocytes interact with activated monocytes that express FasL, resulting in apoptosis, leading to deletion of CD4 + T cells, an inversion in the CD4:CD8 T-cell ratio, and immune dysfunction. The prevention of CD4 + T-cell apoptosis and improved immune reconstitution by the manipulation of PB stem cell products, blockade of Fas-FasL interactions, or cytokine support after transplantation may be important adjuvant immunotherapeutic strategies in patients undergoing high-dose chemotherapy and PSCT.