A Large-Scale Method for the Selective Depletion of Alphabeta T Lymphocytes From PBSC for Allogeneic Transplantation

Cytotherapy. 2007;9(8):746-54. doi: 10.1080/14653240701644000. Epub 2007 Oct 4.

Abstract

Background: We sought to develop a method for the clinical large-scale depletion of alphabeta T lymphocytes from mobilized peripheral stem cells, which would allow the allogeneic transplantation of a graft enriched for stem cells, natural killer (NK) cells and gammadelta T lymphocytes.

Methods: Therefore, we obtained mononuclear cells from either mobilized or non-mobilized healthy adult volunteer donors and incubated the cells with a biotinylated anti-alphabeta T-cell Ab and subsequently with an anti-biotin Ab conjugated with magnetic microbeads. The depletion was then performed using a CliniMACS device.

Results: The median T-cell depletion was 3.9 log (range 3.5-4.1 log). The recovery of the gammadelta and NK cells was 92% and 80%, respectively. The recovery of CD34+ stem cells from the mobilized donors was 66%.

Discussion: This method had no negative influence on the in vitro colony formation of stem cells, and transplantation of alphabeta-depleted cells into NOD-SCID IL-2 common gamma chain knockout (NOD-scid IL2r (null)) mice resulted in a rapid engraftment of human myeloid and lymphoid cells. This method will allow large-scale depletion of alphabeta T cells from mobilized peripheral blood in clinical trials.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Hematopoietic Stem Cell Mobilization / methods
  • Humans
  • Immunomagnetic Separation / methods
  • Immunophenotyping
  • Lymphocyte Depletion / methods*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Peripheral Blood Stem Cell Transplantation* / methods
  • Receptors, Antigen, T-Cell, alpha-beta* / immunology
  • T-Lymphocytes* / immunology
  • Transplantation, Homologous

Substances

  • Receptors, Antigen, T-Cell, alpha-beta