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Prepublished online as a Blood First Edition Paper on August 21, 2003; DOI 10.1182/blood-2003-05-1428.

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Submitted May 12, 2003
Accepted July 10, 2003

Evidence for adequate thymic function but impaired naive T-cell survival following allogenic hematopoietic stem cell transplantation in the absence of chronic graft versus host disease

Jean-Francois Poulin, Myriam Sylvestre, Patrick Champagne, Marie-Lise Dion, Nadia Kettaf, Alain Dumont, Maryse Lainesse, Pierre Fontaine, Denis-Claude Roy, Claude Perreault, Rafick-Pierre Sekaly*, and Remi Cheynier

Departement d'Immunologie, Centre de Recherches du CHUM, Montreal, PQ, Canada; Departement de Microbiologie et Immunologie, Faculte de Medecine, Universite de Montreal, Montreal, PQ, Canada; Department of Microbiology and Immunology, McGill University, Montreal, PQ, Canada
Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, PQ, Canada; Departement de Medecine, Centre de Recherche Hopital Maisonneuve-Rosemont, Montreal, PQ, Canada

* Corresponding author; email: rafick-pierre.sekaly{at}umontreal.ca.

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 circles frequencies (both the sjTREC and 6 different D{beta}J{beta} TRECs, by-products of TCR{alpha} and {beta} gene rearrangement respectively), in conjunction with immunophenotype and spectratype analyses in a cohort of patients sampled from one to ten years following AHSCT. In this cohort, reduced thymic function was only associated with ongoing clinical chronic graft versus host disease (cGVHD). Nonetheless, the diversity of thymic production remained unchanged irrespectively of the patient's cGVHD status. Interestingly, increased homeostatic proliferation was found in the naive T cells compartment of transplanted cGVHD- patients. However, reduced expression of both the IL-7R{alpha} (CD127) chain and the anti-apoptotic protein Bcl-2 were 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.


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