Umbilical cord blood T cells cultured with IL-7 in addition to IL-2 exhibit a higher degree of polyfunctionality and superior proliferation potential
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1
Karolinska Institute, Dept of Laboratory Medicine, Sweden
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2
Karolinska University Hospital Huddinge, Centre for Allogeneic Stem cell Transplantation (CAST), Sweden
BACKGROUND: Umbilical cord blood transplantation (UCBT) is an increasingly used stem cell source for allogeneic stem cell transplantation. One disadvantage to UCBT is that treatment with donor lymphocyte infusion (DLI) is not possible. We wanted to explore if cultured T cells from the UCB graft could offer an alternative to DLI in this setting. METHODS: T cells were positively selected with CD3+/CD28+ magnetic beads and cultured with IL-2 at escalating concentrations. In addition, IL-7 (20 ng/ml) was added to half of the cultures. After 7 days of expansion the T cells were analyzed by flow cytometry to determine phenotype, and cytokine production.
RESULTS: There was significantly greater proliferation in cultures to which IL-7 had been added. Phenotypical differeces such as a higher CD4+/CD8+, a lower percentage of central memory T cells (CD45RO+ CCR7+) and a higher percentage of effector memory T cells (CD45RO+ CCR7-) was seen with IL-7. We assessed the intracellular production of IL-2, TNF-alpha, IFN-gamma and CD107a, and found that a higher percentage of polyfunctional T cells (positive for three or four factors) was seen in cells cultured with IL-7 in CD3+ and CD3+CD8+ cells, with a trend towards the same association also in CD3+CD4+ cells.
CONCLUSION: There seem to be a proliferation advantage in adding IL-7 to a lower dose of IL-2. Addition of IL-7 also seem to have an impact on the differentiation status of the cells. T cells cultured in IL-7 had more polyfunctional traits, possibly increasing the activity of a putative future DLI.
Acknowledgements
The authors would like to thank the maternity ward, in particular Boel Niklasson, at Karolinska University hospital Huddinge, Stockholm, Sweden, for their kind assistance in obtaining the umbilical cord blood units. This study was supported by grants from Swedish Research Council (K2012-64X-22020-01-3) and The Swedish Childhood Cancer Foundation (PROJ10/052) and Swedish society for medical research.
Keywords:
umbilical cord blood,
IL-7,
T cell expansion,
DLI,
Cell Culture Techniques
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Translational immunology and immune intervention
Citation:
Berglund
S,
Gertow
J,
Magalhaes
I,
Uhlin
M and
Mattsson
J
(2013). Umbilical cord blood T cells cultured with IL-7 in addition to IL-2 exhibit a higher degree of polyfunctionality and superior proliferation potential.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00697
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Received:
12 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Sofia Berglund, Karolinska Institute, Dept of Laboratory Medicine, Stockholm, 14186, Sweden, sofia.berglund@ki.se