Identification of non-naïve CD4+CD45RA+ T cell subsets in adult allogeneic haematopoietic cell transplant recipients

Bone Marrow Transplant. 2003 Sep;32(6):609-16. doi: 10.1038/sj.bmt.1704185.

Abstract

The study of thymic-dependent pathways of T cell reconstitution in T cell replete haematopoietic cell transplant (HCT) recipients in previous studies was complicated by the transfer of naïve CD4(+)CD45RA(+) T cells with the stem cell graft. However, direct quantification of thymic output has been enabled by measurement of T cell receptor excision circles (TREC). We analysed T cell reconstitution using T cell phenotyping and TREC quantification in 12 T cell-replete HCT recipients 6-53 years of age during the first 12 months post transplant. We have identified a novel subpopulation of CD4(+)CD45RA(+) T cells in the peripheral blood of these HCT recipients with expansions of this subset being more pronounced in older recipients. The recovery of classical naïve CD4(+)CD45RA(+) T cells was dependent on thymic output whereas this novel CD4(+)CD45RA(+) subpopulation arose independently of thymic output and displayed effector function and phenotype. These results suggest that CD4(+)CD45RA(+) effector populations exist, similar to the CD8(+)CD45RA(+) effector subset, and that the CD45RA antigen should not be used alone to define naïve CD4(+) T cells when monitoring T cell reconstitution in T cell replete HCT recipients. Furthermore, these results raise important questions regarding the role of the thymus in regulating T cell homeostasis in older HCT recipients and normal individuals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • CD4 Antigens / analysis
  • Child
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immune System / cytology
  • Immune System / physiology
  • Immunophenotyping
  • Leukocyte Common Antigens / analysis
  • Lymphocyte Depletion
  • Middle Aged
  • Receptors, Antigen, T-Cell / analysis
  • Regeneration*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / physiology*
  • Thymus Gland / physiology*
  • Transplantation, Homologous

Substances

  • CD4 Antigens
  • Receptors, Antigen, T-Cell
  • Leukocyte Common Antigens