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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{beta}J{beta} TRECs, by-products of T-cell receptor [TCR] {alpha} and {beta} 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 {alpha} (IL-7R{alpha}) (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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