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Blood, 15 December 2003, Vol. 102, No. 13, pp. 4600-4607.
Prepublished online as a Blood First Edition Paper on August 21, 2003; DOI 10.1182/blood-2003-05-1428.
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TRANSPLANTATION
Evidence for adequate thymic function but impaired naive T-cell survival following allogeneic hematopoietic stem cell transplantation in the absence of chronic graft-versus-host disease
Jean-François Poulin,
Myriam Sylvestre,
Patrick Champagne,
Marie-Lise Dion,
Nadia Kettaf,
Alain Dumont,
Maryse Lainesse,
Pierre Fontaine,
Denis-Claude Roy,
Claude Perreault,
Rafick-Pierre Sékaly, and
Rémi Cheynier
From the Laboratoire d'Immunologie, Centre de Recherches du Centre Hospitalier de l'Université de Montréal (CHUM), Hôtel-Dieu, Montréal, QC; the Department of Medicine, Division of Experimental Medicine, and the Department of Microbiology and Immunology, McGill University, Montréal, QC; the Département de Microbiologie et Immunologie, Faculté de Médecine, Université de Montréal, QC; and the Département de Médecine, Université de Montréal and Centre de Recherche Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada.
Allogeneic hematopoietic stem cell transplantation (AHSCT) leads to a prolonged state of immunodeficiency characterized by low peripheral naive T-cell counts. To identify the mechanisms leading to this defect we quantitatively and qualitatively analyzed thymic function through quantification of T-cell receptor excision circle (TREC) frequencies (both the signal-joint TREC [sjTREC] and 6 different D J TRECs, by-products of T-cell receptor [TCR] and gene rearrangement, respectively), in conjunction with immunophenotype and spectratype analyses in a cohort of patients sampled from 1 to 10 years following AHSCT. In this cohort, reduced thymic function was associated only with ongoing clinical chronic graft-versus-host disease (cGVHD). Nonetheless, the diversity of thymic production remained unchanged irrespective of the patient's cGVHD status. Interestingly, increased homeostatic proliferation was found in the naive T-cell compartment of cGVHD- patients who underwent transplantation. However, reduced expression of both the interleukin-7 receptor (IL-7R ) (CD127) chain and the antiapoptotic protein Bcl-2 was observed. Taken together, these data indicate that the inability to reconstitute the naive T-cell compartment for several years after AHSCT, in the absence of cGVHD, is a consequence of impaired naive T-cell survival rather than thymic dysfunction. (Blood. 2003;102:4600-4607)

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