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 journalArticle

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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

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Fas Ligand Protein
Stem Cell Transplantation
Apoptosis
T-Lymphocytes
Peripheral Blood Stem Cell Transplantation
Monocytes
Drug Therapy
Transplantation
Lymphocytes
Breast Neoplasms
Cytokines

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Singh, R. K., Varney, M. L., Buyukberber, S., Ino, K., Ageitos, A. G., Reed, E., ... Talmadge, J. E. (1999). Fas-FasL-mediated CD4+ T-cell apoptosis following stem cell transplantation. Cancer Research, 59(13), 3107-3111.

Fas-FasL-mediated CD4+ T-cell apoptosis following stem cell transplantation. / Singh, Rakesh K.; Varney, Michelle L.; Buyukberber, Suleyman; Ino, Kazuhiko; Ageitos, Ana G.; Reed, Elizzabeth; Tarantolo, Stefano; Talmadge, James E.

In: Cancer Research, Vol. 59, No. 13, 01.07.1999, p. 3107-3111.

Research output: Contribution to journalArticle

Singh, RK, Varney, ML, Buyukberber, S, Ino, K, Ageitos, AG, Reed, E, Tarantolo, S & Talmadge, JE 1999, 'Fas-FasL-mediated CD4+ T-cell apoptosis following stem cell transplantation', Cancer Research, vol. 59, no. 13, pp. 3107-3111.
Singh RK, Varney ML, Buyukberber S, Ino K, Ageitos AG, Reed E et al. Fas-FasL-mediated CD4+ T-cell apoptosis following stem cell transplantation. Cancer Research. 1999 Jul 1;59(13):3107-3111.
Singh, Rakesh K. ; Varney, Michelle L. ; Buyukberber, Suleyman ; Ino, Kazuhiko ; Ageitos, Ana G. ; Reed, Elizzabeth ; Tarantolo, Stefano ; Talmadge, James E. / Fas-FasL-mediated CD4+ T-cell apoptosis following stem cell transplantation. In: Cancer Research. 1999 ; Vol. 59, No. 13. pp. 3107-3111.
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