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.
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 DbetaJbeta 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-7Ralpha) (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.
Poulin
Jean-François
JF
Laboratoire d'Immunologie, Département de Microbiologie et Immunologie, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montréal (QC) H3C 3J7, Canada.
Sylvestre
Myriam
M
Champagne
Patrick
P
Dion
Marie-Lise
ML
Kettaf
Nadia
N
Dumont
Alain
A
Lainesse
Maryse
M
Fontaine
Pierre
P
Roy
Denis-Claude
DC
Perreault
Claude
C
Sékaly
Rafick-Pierre
RP
Cheynier
Rémi
R
D000328:Adult; D000368:Aged; D002455:Cell Division; D002470:Cell Survival; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008231:Lymphopenia / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000172:deficiency; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D020395:Receptors, Interleukin-7 / Q000172:deficiency; D013601:T-Lymphocytes / Q000473:pathology*; D013950:Thymus Gland / Q000502:physiology*
D019253:Proto-Oncogene Proteins c-bcl-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain