A broad T-cell repertoire diversity and an efficient thymic function indicate a favorable long-term immune reconstitution after cord blood stem cell transplantation

Author:

Talvensaari Kimmo1,Clave Emmanuel1,Douay Corinne1,Rabian Claire1,Garderet Laurent1,Busson Marc1,Garnier Federico1,Douek Daniel1,Gluckman Eliane1,Charron Dominique1,Toubert Antoine1

Affiliation:

1. From the 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; and Vaccine Research Center, NIAD (National Institute of Allergy and Infectious Diseases) and Department of Experimental Transplantation and Immunology, National Cancer Institute, National Institutes of Health, Bethesda, MD.

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 αβ 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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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