Factors affecting reconstitution of the T cell compartment in allogeneic haematopoietic cell transplant recipients

Bone Marrow Transplant. 2003 Nov;32(10):1001-14. doi: 10.1038/sj.bmt.1704235.

Abstract

The factors affecting T cell reconstitution post haematopoietic cell transplantation (HCT) are not well characterised. We carried out a longitudinal analysis of T cell reconstitution in 32 HCT recipients during the first 12 months post transplant. We analysed reconstitution of naïve, memory and effector T cells, their diversity and monitored thymic output using TCR rearrangement excision circles (TRECs). Thymic-independent pathways were responsible for the rapid reconstitution of memory and effector T cells less than 6 months post HCT. Thymic-dependent pathways were activated between 6 and 12 months in the majority of patients with naïve T cell numbers increasing in parallel with TREC levels. Increasing patient age, chronic GVHD and T cell depletion (with or without pretransplant Campath-1H) predicted low TREC levels and slow naïve T cell recovery. Furthermore, increasing patient age also predicted high memory and effector T cell numbers. The effects of post HCT immunosuppression, total body irradiation, donor leucocyte infusions, T cell dose and post HCT infections on T cell recovery were also analysed. However, no effects of these single variables across a variety of different age, GVHD and T cell depletion groups were apparent. This study suggests that future analysis of the factors affecting T cell reconstitution and studies aimed at reactivating the thymus through therapeutic intervention should be analysed in age-, GVHD- and TCD-matched patient groups.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Blood Cells
  • Child
  • Graft vs Host Disease
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Longitudinal Studies
  • Lymphocyte Count
  • Lymphocyte Depletion
  • Lymphopoiesis
  • Middle Aged
  • Receptors, Antigen, T-Cell / analysis
  • Regeneration*
  • T-Lymphocyte Subsets
  • T-Lymphocytes / physiology*
  • Thymus Gland / physiology
  • Transplantation, Homologous

Substances

  • Receptors, Antigen, T-Cell