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

We report the preferential expression of Fat; on CD4(+) T cells and Fas Lig and (FasL) on monocytes and their potential role in the selective loss of C D4(+) T cells in breast cancer patients underlying 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 aft er PSCT concomitant with a significant increase in monocyte frequency and F asL 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 i s associated with a significantly higher frequency of CD4(+) T-cell apoptos is compared with CD8(+) T cells (28-47%) and CD4(+) T cells (46 +/- 5.7%) i n normal PB, These data suggest that "primed" Fas(+) CD4(+) lymphocytes int eract with activated monocytes that express Fast, resulting in apoptosis, l eading to deletion of CD4(+) T cells, an inversion in the CD4:CD8 T-cell ra tio, 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 transplantat ion may be important adjuvant immunotherapeutic strategies in patients unde rgoing high-dose chemotherapy and PSCT.