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


CONCLUSIONS
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.
Chaleff
S
S
Division of Stem Cell Transplantation, Department of Hematology-Oncology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
Otto
M
M
Barfield
R C
RC
Leimig
T
T
Iyengar
R
R
Martin
J
J
Holiday
M
M
Houston
J
J
Geiger
T
T
Huppert
V
V
Handgretinger
R
R
D000328:Adult; D000818:Animals; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006801:Humans; D018189:Immunomagnetic Separation / Q000379:methods; D016130:Immunophenotyping; D008212:Lymphocyte Depletion / Q000379:methods*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
D016693:Receptors, Antigen, T-Cell, alpha-beta