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

Br J Haematol. 2003 Sep;122(6):934-43. doi: 10.1046/j.1365-2141.2003.04522.x.

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.

MeSH terms

  • Adolescent
  • Adult
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Division / immunology
  • Child
  • Female
  • Flow Cytometry / methods
  • Graft vs Host Disease / immunology*
  • Hematologic Neoplasms / therapy*
  • Humans
  • Immunity, Cellular
  • Immunophenotyping / methods
  • Lymphocyte Subsets / immunology
  • Male
  • Middle Aged
  • Peripheral Blood Stem Cell Transplantation / methods*
  • T-Lymphocyte Subsets / immunology*
  • Thymus Gland / immunology
  • Transplantation Chimera / immunology