title: CXCR4-related increase of circulating human lymphoid progenitors after allogeneic hematopoietic stem cell transplantation.
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.
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France; INSERM UMR1160, Paris, France; Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint-Louis, AP-HP, Paris, France.
authors.forename: Salomé
authors.initials: S
authors.lastname: Glauzy
authors.affiliation: INSERM U768, Université Paris Descartes, Sorbonne Paris Cité, Institut Imagine, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: André-Schmutz
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France; INSERM UMR1160, Paris, France; Unité de Thérapie Cellulaire et CIC de Biothérapies, Hôpital Saint-Louis, AP-HP, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Larghero
authors.affiliation: INSERM, Unité 1020, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Ezine
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France; Service d'Hématologie-Greffe de Moelle, Hôpital Saint-Louis, AP-HP, Paris, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Peffault de Latour
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France; INSERM UMR1160, Paris, France; Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint-Louis, AP-HP, Paris, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Moins-Teisserenc
authors.affiliation: Service d'Hématologie-Greffe de Moelle, Hôpital Saint-Louis, AP-HP, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Servais
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France; Service d'Hématologie-Greffe de Moelle, Hôpital Saint-Louis, AP-HP, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Robin
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France; INSERM UMR1160, Paris, France; Service d'Hématologie-Greffe de Moelle, Hôpital Saint-Louis, AP-HP, Paris, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France; INSERM UMR1160, Paris, France; Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint-Louis, AP-HP, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Clave
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, Institut Universitaire d'Hématologie, Paris, France; INSERM UMR1160, Paris, France; Laboratoire d'Immunologie et d'Histocompatibilité, Hôpital Saint-Louis, AP-HP, Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology; D054377:Chemokine CXCL12 / Q000378:metabolism; D002648:Child; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006789:Host vs Graft Reaction / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015260:Neprilysin / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology; D014184:Transplantation, Homologous / Q000009:adverse effects; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D015260:Neprilysin