A large-scale method for the selective depletion of alphabeta T lymphocytes from PBSC for allogeneic transplantation

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. Therefore, we obtained mo...

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Bibliographic Details
Published in:Cytotherapy (Oxford, England) England), 2007, Vol.9 (8), p.746-754
Main Authors: Chaleff, S, Otto, M, Barfield, R C, Leimig, T, Iyengar, R, Martin, J, Holiday, M, Houston, J, Geiger, T, Huppert, V, Handgretinger, R
Format: Article
Language:English
Subjects:
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
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Summary: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. 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. 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%. 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.
ISSN:1477-2566