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Blood, 15 February 2002, Vol. 99, No. 4, pp. 1458-1464
TRANSPLANTATION
A broad T-cell repertoire diversity and an efficient thymic
function indicate a favorable long-term immune reconstitution after
cord blood stem cell transplantation
Kimmo Talvensaari,
Emmanuel Clave,
Corinne Douay,
Claire Rabian,
Laurent Garderet,
Marc Busson,
Federico Garnier,
Daniel Douek,
Eliane Gluckman,
Dominique Charron, and
Antoine Toubert
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.
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   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.
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