title: Early reconstitution of the T-cell repertoire after non-myeloablative peripheral blood stem cell transplantation is from post-thymic T-cell expansion and is unaffected by graft-versus-host disease or mixed chimaerism.
abstract: To study immune recovery after non-myeloablative, reduced-intensity stem cell allografts (NST) and T-cell-depleted myeloablative transplants (TCD), we measured T-cell subset recovery by flow cytometry, T-cell repertoire by spectratyping and thymic T-cell output using a T-cell receptor excision circle (TREC) assay. We found a rapid and comparable increase in lymphocyte numbers in both NST and TCD, supporting the presence of a powerful drive for lymphocyte recovery after transplant. Spectratyping on d 45 and 100 revealed almost complete normalization of the T-cell repertoire in NST patients by d 45, whereas TCD patients demonstrated marked skewing of the repertoire, persisting to d 100. After NST, there was a significantly higher number of TREC-positive CD4+ and CD8+ cells (P = 0.02 and P = 0.01 respectively). However, in both NST and TCD, early T-cell recovery after transplant appeared to result entirely from post-thymic T cells, the expansion pattern of which is most influenced by the starting T-cell dose, but not markedly by graft-versus-host disease (GVHD) or mixed chimaerism. These results define important qualitative differences in the T-cell repertoire according to the type of transplant schedule used.
authors.affiliation: Bone Marrow Transplant Unit, Hematology Branch, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Erkut
authors.initials: E
authors.lastname: Bahceci
authors.forename: Diane
authors.initials: D
authors.lastname: Epperson
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: J Joseph
authors.initials: JJ
authors.lastname: Melenhorst
authors.forename: Richard C
authors.initials: RC
authors.lastname: Childs
authors.forename: A John
authors.initials: AJ
authors.lastname: Barrett
mesh_terms: D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002648:Child; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006086:Graft vs Host Disease / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000628:therapy*; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping / Q000379:methods; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology