CXCR4-related increase of circulating human lymphoid progenitors after allogeneic hematopoietic stem cell transplantation

PLoS One. 2014 Mar 12;9(3):e91492. doi: 10.1371/journal.pone.0091492. eCollection 2014.

Abstract

Immune recovery after profound lymphopenia is a major challenge in many clinical situations, such as allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recovery depends, in a first step, on hematopoietic lymphoid progenitors production in the bone marrow (BM). In this study, we characterized CD34+Lin-CD10+ lymphoid progenitors in the peripheral blood of allo-HSCT patients. Our data demonstrate a strong recovery of this population 3 months after transplantation. This rebound was abolished in patients who developed acute graft-versus-host disease (aGVHD). A similar recovery profile was found for both CD24+ and CD24- progenitor subpopulations. CD34+lin-CD10+CD24- lymphoid progenitors sorted from allo-HSCT patients preserved their T cell potentiel according to in vitro T-cell differentiation assay and the expression profile of 22 genes involved in T-cell differentiation and homing. CD34+lin-CD10+CD24- cells from patients without aGVHD had reduced CXCR4 gene expression, consistent with an enhanced egress from the BM. CCR7 gene expression was reduced in patients after allo-HSCT, as were its ligands CCL21 and CCL19. This reduction was particularly marked in patients with aGVHD, suggesting a possible impact on thymic homing. Thus, the data presented here identify this population as an important early step in T cell reconstitution in humans and so, an important target when seeking to enhance immune reconstitution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD34 / metabolism
  • Bone Marrow Cells / immunology
  • Chemokine CXCL12 / metabolism
  • Child
  • Down-Regulation / immunology
  • Female
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Host vs Graft Reaction / immunology
  • Humans
  • Male
  • Middle Aged
  • Neprilysin / metabolism
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism*
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Thymus Gland / immunology
  • Transplantation, Homologous / adverse effects
  • Young Adult

Substances

  • Antigens, CD34
  • Chemokine CXCL12
  • Receptors, CXCR4
  • Neprilysin

Grants and funding

This work was supported by research grants from Assistance Publique–Hôpitaux de Paris (#RTB10002), LABEX Milieu Intérieur, LABEX Transplantex, ERA-NET program TRANSCAN 12-072 HAPLO-IMMUNE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.