Expansion of Gammadelta T Cells from Cord Blood: A Therapeutical Possibility

Gammadelta (γδ) T cells are found in both blood and tissues and have antiviral and antitumor properties. The frequency of γδ T cells in umbilical cord blood (UCB) is low, and the majority express δ1, in contrast to blood, whereas the main subset is δ2γ9 T cells. UCB γδ T cells are functionally immat...

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Main Authors: Sofia Berglund, Ahmed Gaballa, Piamsiri Sawaisorn, Berit Sundberg, Michael Uhlin
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2018/8529104
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author Sofia Berglund
Ahmed Gaballa
Piamsiri Sawaisorn
Berit Sundberg
Michael Uhlin
author_facet Sofia Berglund
Ahmed Gaballa
Piamsiri Sawaisorn
Berit Sundberg
Michael Uhlin
author_sort Sofia Berglund
collection DOAJ
description Gammadelta (γδ) T cells are found in both blood and tissues and have antiviral and antitumor properties. The frequency of γδ T cells in umbilical cord blood (UCB) is low, and the majority express δ1, in contrast to blood, whereas the main subset is δ2γ9 T cells. UCB γδ T cells are functionally immature, which together with their scarcity complicates the development of UCB γδ T cell therapies. We aimed to develop an effective expansion protocol for UCB γδ T cells based on zoledronate and IL-2. We found that culture with 5 μM zoledronate and 200 IU IL-2/ml medium for 14 days promoted extensive proliferation. The majority of the cultured cells were γ9δ2 T cells. The fold expansion of this, originally infrequent, subset was impressive (median and maximum fold change 253 and 1085, resp.). After culture, the cells had a polyclonal γδ T cell repertoire and the main memory subset was central memory (CD45RO+ CD27+). The cells produced cytokines such as IL-1B, IL-2, and IL-8 and displayed significant tumor-killing capacity. These results show that development of in vitro expanded UCB γδ T cell therapies is feasible. It could prove a valuable treatment modality for patients after umbilical cord blood transplantation.
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spelling doaj-art-b7ca8dbf32a44a2798799389e67a22f72025-02-03T01:22:19ZengWileyStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/85291048529104Expansion of Gammadelta T Cells from Cord Blood: A Therapeutical PossibilitySofia Berglund0Ahmed Gaballa1Piamsiri Sawaisorn2Berit Sundberg3Michael Uhlin4Department of Medicine, Solna, Karolinska Institutet, Stockholm, SwedenDepartment of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, SwedenDepartment of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, SwedenDepartment of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, SwedenDepartment of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, SwedenGammadelta (γδ) T cells are found in both blood and tissues and have antiviral and antitumor properties. The frequency of γδ T cells in umbilical cord blood (UCB) is low, and the majority express δ1, in contrast to blood, whereas the main subset is δ2γ9 T cells. UCB γδ T cells are functionally immature, which together with their scarcity complicates the development of UCB γδ T cell therapies. We aimed to develop an effective expansion protocol for UCB γδ T cells based on zoledronate and IL-2. We found that culture with 5 μM zoledronate and 200 IU IL-2/ml medium for 14 days promoted extensive proliferation. The majority of the cultured cells were γ9δ2 T cells. The fold expansion of this, originally infrequent, subset was impressive (median and maximum fold change 253 and 1085, resp.). After culture, the cells had a polyclonal γδ T cell repertoire and the main memory subset was central memory (CD45RO+ CD27+). The cells produced cytokines such as IL-1B, IL-2, and IL-8 and displayed significant tumor-killing capacity. These results show that development of in vitro expanded UCB γδ T cell therapies is feasible. It could prove a valuable treatment modality for patients after umbilical cord blood transplantation.http://dx.doi.org/10.1155/2018/8529104
spellingShingle Sofia Berglund
Ahmed Gaballa
Piamsiri Sawaisorn
Berit Sundberg
Michael Uhlin
Expansion of Gammadelta T Cells from Cord Blood: A Therapeutical Possibility
Stem Cells International
title Expansion of Gammadelta T Cells from Cord Blood: A Therapeutical Possibility
title_full Expansion of Gammadelta T Cells from Cord Blood: A Therapeutical Possibility
title_fullStr Expansion of Gammadelta T Cells from Cord Blood: A Therapeutical Possibility
title_full_unstemmed Expansion of Gammadelta T Cells from Cord Blood: A Therapeutical Possibility
title_short Expansion of Gammadelta T Cells from Cord Blood: A Therapeutical Possibility
title_sort expansion of gammadelta t cells from cord blood a therapeutical possibility
url http://dx.doi.org/10.1155/2018/8529104
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AT beritsundberg expansionofgammadeltatcellsfromcordbloodatherapeuticalpossibility
AT michaeluhlin expansionofgammadeltatcellsfromcordbloodatherapeuticalpossibility