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

Rakesh K. Singh, Michelle L. Varney, Suleyman Buyukberber, Kazuhiko Ino, Ana G. Ageitos, Elizzabeth Reed, Stefano Tarantolo, James E. Talmadge

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3107-3111
Number of pages5
JournalCancer Research
Volume59
Issue number13
StatePublished - Jul 1 1999

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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