title: A broad T-cell repertoire diversity and an efficient thymic function indicate a favorable long-term immune reconstitution after cord blood stem cell transplantation.
abstract: Cord blood (CB) is used increasingly as a source of hematopoietic stem cells because of a lower risk of acute and chronic graft-versus-host disease (GVHD). However, there is some concern regarding the ability to adequately reconstitute host immune response due to the immaturity and naivety of CB T cells. This study was designed to evaluate T-cell reconstitution using combined approaches of phenotyping, analysis of alphabeta T-cell receptor (TCR) diversity, and assessment of ex vivo thymic function by measuring TCR rearrangement excision circles (TRECs). Ten patients who underwent CB transplantation for high-risk hematologic disorders were compared to a reference group of 19 age- and GVHD-matched patients who underwent transplantation with non-T cell-depleted bone marrow from an HLA-identical sibling donor. TREC values correlated with the relative number of naive T cells and with TCR repertoire polyclonality. During the first year after transplantation, TCR repertoires were highly abnormal and TREC values low in both groups. Notably, 2 years after transplantation onward TREC values as well as TCR diversity were higher in CB recipients than in recipients of bone marrow transplants. These data indicate an efficient thymic regeneration pathway from CB lymphoid progenitors despite the low number of cells infused compared to bone marrow, arguing for a complete clinical immune recovery after CB transplantation.
authors.affiliation: Laboratoire d'Immunologie et d'Histocompatibilité, INSERM U.396, Institut Universitaire d'Hématologie; Service d'Hématologie-Greffe de Moelle, Hôpital Saint-Louis, AP-HP, Paris, France.
authors.forename: Kimmo
authors.initials: K
authors.lastname: Talvensaari
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Clave
authors.forename: Corinne
authors.initials: C
authors.lastname: Douay
authors.forename: Claire
authors.initials: C
authors.lastname: Rabian
authors.forename: Laurent
authors.initials: L
authors.lastname: Garderet
authors.forename: Marc
authors.initials: M
authors.lastname: Busson
authors.forename: Federico
authors.initials: F
authors.lastname: Garnier
authors.forename: Daniel
authors.initials: D
authors.lastname: Douek
authors.forename: Eliane
authors.initials: E
authors.lastname: Gluckman
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D005260:Female; D005312:Fetal Blood; D005500:Follow-Up Studies; D006087:Graft vs Host Reaction / Q000276:immunology; D006402:Hematologic Diseases / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007107:Immune System / Q000166:cytology*; D016130:Immunophenotyping; D019891:Leukopoiesis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta