Omission of in vivo T-cell depletion promotes rapid expansion of naïve CD4+ cord blood lymphocytes and restores adaptive immunity within 2 months after unrelated cord blood transplant

Br J Haematol. 2012 Mar;156(5):656-66. doi: 10.1111/j.1365-2141.2011.08994.x. Epub 2012 Jan 9.

Abstract

Umbilical cord blood transplant (UCBT) is associated with impaired early immune reconstitution. This might be explained by a lower T-cell dose infused, the naivety of cord blood T-cells and the use of in vivo T-cell depletion. We studied the pattern of early immune reconstitution and the clinical outcome of children undergoing unrelated UCBT when in vivo T-cell depletion was omitted. Thirty children affected by malignancies (46%) or immunodeficiencies (54%) underwent an unrelated UCBT. Prospective assessment of immune reconstitution and clinical outcome was performed. We observed an unprecedented CD4(+) T-cell reconstitution, with a median cell count at 30 and 60 d post UCBT of 0.3 × 10(9) /l and 0.56 × 10(9) /l, respectively. Early T-cell expansion was thymic-independent, with a rapid shift from naïve to central memory phenotype and early regulatory T-cell recovery. Viral infections were frequent (63%) but resolved rapidly in most cases and virus-specific T-lymphocytes were detected within 2 months post-UCBT. Acute graft-versus-host disease (GvHD) was frequent (grade II = 34%, grade III-IV = 16%) but steroid responsive, and the incidence of chronic GvHD was low (14%). The omission of in vivo T-cell depletion promotes a unique thymic-independent CD4(+) T-cell reconstitution after unrelated UCBT in children. We postulate that this relates to the specific immunological and ontological qualities of fetal-derived lymphocytes.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • B-Lymphocytes / immunology
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology*
  • Child
  • Child, Preschool
  • Cord Blood Stem Cell Transplantation / adverse effects
  • Cord Blood Stem Cell Transplantation / methods*
  • Female
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control
  • Humans
  • Immunologic Memory
  • Immunophenotyping
  • Infant
  • Killer Cells, Natural / immunology
  • Lymphocyte Count
  • Lymphocyte Depletion
  • Male
  • Opportunistic Infections / immunology
  • Opportunistic Infections / prevention & control
  • T-Lymphocytes, Regulatory / immunology
  • Treatment Outcome