Dual roles of autologous CD8+ T cells in hematopoietic progenitor cell mobilization and engraftment

Transfusion. 2015 Jul;55(7):1758-65; quiz 1757. doi: 10.1111/trf.13073. Epub 2015 Mar 11.

Abstract

Background: Poor marrow cellularity alone cannot explain poor hematopoietic progenitor cell (HPC) mobilization. This study assessed the role of CD8+ T cells in HPC cell mobilization and engraftment.

Study design and methods: Mobilization and engraftment were assessed in 192 autologous HPC donors. CD34+, CD4+, and CD8+ T-cell contents in apheresis products were evaluated. Using a chemotaxis assay, we assessed the effect of purified autologous CD8+ T cells from low and high mobilizers on HPC migration from high to low stromal cell-derived factor (SDF-1α) concentration gradients. We also assessed CD8+ T-cell content association with days to neutrophil engraftment.

Results: The median number of CD34+ cells/kg was 4.7 × 10(6) . Patients were categorized according to their total CD34+ cell collection quartile distribution into low, moderate, and high mobilizers. We found that HPC products from low mobilizers contained more CD8+ T cells than HPC products from moderate and high mobilizers. Chemotaxis assays showed depletion of CD8+ T cells enhances HPC mobilization independent of SDF-1α concentration. Neutrophil engraftment analysis showed that the higher the CD8+ T-cell content per unit CD34+ cell, the faster the rate of engraftment.

Conclusion: Our findings suggest CD8+ T cells inhibit HPC mobilization and facilitate homing and engraftment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Autografts
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Chemokine CXCL12 / drug effects
  • Chemotaxis / drug effects
  • Chemotaxis / immunology*
  • Female
  • Graft Survival / immunology*
  • Hematopoietic Stem Cell Mobilization*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukapheresis*
  • Male
  • Middle Aged

Substances

  • CXCL12 protein, human
  • Chemokine CXCL12