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.
Highlights
In many clinical situations, such as intensive chemotherapy, acquired immunodeficiencies and allogeneic hematopoietic stem cell transplantation, immune recovery is a major challenge
Month 3 was chosen as the best time point at which to assess the CD34+lin2CD10+CD242 population after allo-HSCT
Circulating progenitors were quantified by flow cytometry in a subgroup of 39 allo-HSCT patients, in 19 age-matched healthy donors (HD), and in 8 cord blood (CB) samples (Fig. S1)
Summary
In many clinical situations, such as intensive chemotherapy, acquired immunodeficiencies and allogeneic hematopoietic stem cell transplantation (allo-HSCT), immune recovery is a major challenge. Complete rescue of immune competence is closely linked to the recovery of de novo T-cell production in the thymus. Six et al [8] characterized two progenitor populations: CD34+Lin2CD10+CD242 cells, with a very low myeloid potential capable of giving rise to B, T and NK lymphocytes; and CD34+Lin2CD10+CD24+ cells, which are already committed to the B-cell lineage. The CD242 population may represent thymusseeding progenitors (TSP) It is found in cord blood (CB), BM, thymus and, importantly, it is detectable in peripheral blood throughout life. These cells express low levels of CD38 and may correspond to the multilymphoid progenitor population (MLP) described by Doulatov et al [9]. The relationship between CD102CD62Lhi and TSP remains to be elucidated
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