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

• Published in: Blood Vol. 102; no. 13; pp. 4600 - 4607
• Main Authors: Poulin, Jean-François, Sylvestre, Myriam, Champagne, Patrick, Dion, Marie-Lise, Kettaf, Nadia, Dumont, Alain, Lainesse, Maryse, Fontaine, Pierre, Roy, Denis-Claude, Perreault, Claude, Sékaly, Rafick-Pierre, Cheynier, Rémi
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.12.2003; The Americain Society of Hematology; American Society of Hematology
• Subjects: Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Cell Division; Cell Survival; Cohort Studies; Female; Follow-Up Studies; Graft vs Host Disease - immunology; Graft vs Host Disease - pathology; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Life Sciences; Lymphopenia - etiology; Male; Medical sciences; Middle Aged; Proto-Oncogene Proteins c-bcl-2 - deficiency; Receptors, Antigen, T-Cell, alpha-beta - analysis; Receptors, Interleukin-7 - deficiency; T-Lymphocytes - pathology; Thymus Gland - physiology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Human; Immunopathology; Thymopoiesis; Pathogenesis; Stem cell; T-Lymphocyte; Hematopoietic cell; Homograft; Graft; Naive cell; Immune deficiency
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2003-05-1428

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 DβJβ TRECs, by-products of T-cell receptor [TCR] α and β 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 α (IL-7Rα) (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)