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


CONCLUSIONS
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.
Parmar
S
S
The Department of Blood and Marrow Transplantation, MD Anderson Cancer Center, Houston, Texas, USA.
Robinson
S N
SN
Komanduri
K
K
St John
L
L
Decker
W
W
Xing
D
D
Yang
H
H
McMannis
J
J
Champlin
R
R
de Lima
M
M
Molldrem
J
J
Rieber
A
A
Bonyhadi
M
M
Berenson
R
R
Shpall
E J
EJ
D015703:Antigens, CD / Q000378:metabolism*; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation; D005312:Fetal Blood / Q000166:cytology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
D015703:Antigens, CD; D018106:CD28 Antigens; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell