Programmed Death 1 Expression on CD4+ T Cells Predicts Mortality after Allogeneic Stem Cell Transplantation

Biol Blood Marrow Transplant. 2016 Dec;22(12):2172-2179. doi: 10.1016/j.bbmt.2016.08.007. Epub 2016 Aug 9.


Excessive or persistent programmed death 1 (PD-1) expression on virus- or tumor-specific T cells during chronic viral infection or malignancy has been associated with impaired immune control. To assess the role of the PD-1 pathway in allogeneic stem cell transplantation (SCT), we examined PD-1 expression and maturation phenotype on T cells from 42 patients early (day 55 to 85) after cord blood (CB), matched unrelated donor, and matched related donor transplantation. Expression of PD-1 on CD4+ T cells was significantly elevated in all transplantation types, with the highest level observed in CB subjects. Elevated PD-1 expression on CD4+ T cells early after transplantation was observed in nonsurvivors (median, 40.2%; range, 15.1 to 86.1) compared with survivors (median, 23.6%; range, 8.4 to 55.2; P = .001), indicating its association with increased risk for mortality, especially with CB transplantations, where PD-1 was increased in nonsurvivors (median, 64.6%; range, 36.5 to 86.1) compared with survivors (median, 34.1%; range, 15.9 to 55.2; P = .01). Furthermore, T cell subset analysis revealed that PD-1 expression was further elevated on CD4+ T central memory in nonsurvivors (median, 49.8%; range, 15.1 to 83.4) compared with survivors (median, 24.8%; range, 8.9 to 71.3; P = .002) and on T effector memory cells in nonsurvivors (median, 69.1%; range, 24.7 to 92.6) compared with survivors (median, 43.7%; range, 13.9 to 96.5; P = .0003). Our findings suggest that elevation of PD-1 expression on CD4+ T cells is associated with mortality in CB and possibly all SCT recipients.

Keywords: Allogeneic stem cell transplantation; CD4(+) T cells; Cord blood; Programmed death 1 (PD-1) expression.

MeSH terms

  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / chemistry*
  • Cord Blood Stem Cell Transplantation / methods*
  • Cord Blood Stem Cell Transplantation / mortality
  • Humans
  • Middle Aged
  • Mortality
  • Prognosis
  • Programmed Cell Death 1 Receptor / analysis*
  • Survivors
  • T-Lymphocyte Subsets / chemistry
  • Transplantation, Homologous
  • Young Adult


  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor