Ex vivo expanded umbilical cord blood T cells maintain naive phenotype and TCR diversity

Cytotherapy. 2006;8(2):149-57. doi: 10.1080/14653240600620812.

Abstract

Background: Umbilical cord blood (CB) is a promising source of hematopoietic stem cells for allogeneic transplantation. However, delayed engraftment and impaired immune reconstitution remain major limitations. Enrichment of donor grafts with CB T cells expanded ex vivo might facilitate improved T-cell immune reconstitution post-transplant. We hypothesized that CB T cells could be expanded using paramagnetic microbeads covalently linked to anti-CD3 and anti-CD28 Ab.

Methods: CB units were divided into three fractions: (1) cells cultured without beads, (2) cells cultured with beads and (3) cells cultured with beads following CD3+ magnetic enrichment. All fractions were cultured for 14 days in the presence of IL-2 (200 IU/mL).

Results: A mean 100-fold expansion (range 49-154) of total nucleated cells was observed in the CD3+ magnetically enriched fraction. Following expansion, CB T cells retained a naive and/or central memory phenotype and contained a polyclonal TCR diversity demonstrated by spectratyping.

Discussion: Our data provide evidence that naive and diverse CB T cells may be expanded ex vivo and warrant additional studies in the setting of human CB transplantation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, CD / metabolism*
  • CD28 Antigens / metabolism
  • CD3 Complex / metabolism
  • CD4 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Cells, Cultured
  • Cord Blood Stem Cell Transplantation
  • Fetal Blood / cytology*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Lymphocyte Activation / immunology
  • Receptors, Antigen, T-Cell / metabolism*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*

Substances

  • Antigens, CD
  • CD28 Antigens
  • CD3 Complex
  • CD4 Antigens
  • CD8 Antigens
  • Receptors, Antigen, T-Cell