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In vitro generation of mature, naive antigen-specific CD8⁺ T cells with a single T-cell receptor by agonist selection

(2014) LEUKEMIA. 28(4). p.830-841
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Abstract
Peripheral blood T cells transduced with a tumor-specific T-cell receptor (TCR) face problems of auto-reactivity and lack of efficacy caused by cross-pairing of exogenous and endogenous TCR chains, as well as short term in vivo survival due to activation and growth factor-induced differentiation. We here studied an alternative strategy for the efficient generation of naive CD8(+) T cells with a single TCR. TCR-transduced human postnatal thymus-derived and adult mobilized blood-derived hematopoietic progenitor cells (HPCs) were differentiated to CD4(+)CD8(+) double-positive T cells using OP9-Delta-like 1 (OP9-DL1) cultures. Addition of the agonist peptide induced double positive cells to cross-present the peptide, leading, in the absence of co-stimulation, to cell cycle arrest and differentiation into mature CD8(+) T cells. comprehensive phenotypic, molecular and functional analysis revealed the generation of naive and resting CD8(+) T cells through a process similar to thymic positive selection. These mature T cells show a near complete inhibition of endogenous TCRA and TCRB rearrangements and express high levels of the introduced multimerreactive TCR. Upon activation, specific cytokine production and efficient killing of tumor cells were induced. Using this strategy, large numbers of high-avidity tumor-specific naive T cells can be generated from readily available HPCs without TCR chain cross-pairing.
Keywords
antigen-specific T cell, OP9-DL1, GENE-THERAPY, STEM-CELLS, FUNCTIONAL MATURATION, PROGENITOR CELLS, HUMAN THYMOCYTES, ALPHA-BETA, EXPRESSION, LEUKEMIA, TCR, CANCER, T lymphopoiesis, hematopoietic progenitor cell, adoptive cellular immunotherapy

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MLA
SNAUWAERT, SYLVIA, Greet Verstichel, Sarah Bonte, et al. “In Vitro Generation of Mature, Naive Antigen-specific CD8+ T Cells with a Single T-cell Receptor by Agonist Selection.” LEUKEMIA 28.4 (2014): 830–841. Print.
APA
SNAUWAERT, S., Verstichel, G., Bonte, S., Goetgeluk, G., Vanhee, S., Van Caeneghem, Y., De Mulder, K., et al. (2014). In vitro generation of mature, naive antigen-specific CD8+ T cells with a single T-cell receptor by agonist selection. LEUKEMIA, 28(4), 830–841.
Chicago author-date
SNAUWAERT, SYLVIA, Greet Verstichel, Sarah Bonte, Glenn Goetgeluk, Stijn Vanhee, Yasmine Van Caeneghem, Katrien De Mulder, et al. 2014. “In Vitro Generation of Mature, Naive Antigen-specific CD8+ T Cells with a Single T-cell Receptor by Agonist Selection.” Leukemia 28 (4): 830–841.
Chicago author-date (all authors)
SNAUWAERT, SYLVIA, Greet Verstichel, Sarah Bonte, Glenn Goetgeluk, Stijn Vanhee, Yasmine Van Caeneghem, Katrien De Mulder, Carlo Heirman, Hans Stauss, Miriam HM Heemskerk, Tom Taghon, Georges Leclercq, Jean Plum, Anton W Langerak, Kris Thielemans, Tessa Kerre, and Bart Vandekerckhove. 2014. “In Vitro Generation of Mature, Naive Antigen-specific CD8+ T Cells with a Single T-cell Receptor by Agonist Selection.” Leukemia 28 (4): 830–841.
Vancouver
1.
SNAUWAERT S, Verstichel G, Bonte S, Goetgeluk G, Vanhee S, Van Caeneghem Y, et al. In vitro generation of mature, naive antigen-specific CD8+ T cells with a single T-cell receptor by agonist selection. LEUKEMIA. 2014;28(4):830–41.
IEEE
[1]
S. SNAUWAERT et al., “In vitro generation of mature, naive antigen-specific CD8+ T cells with a single T-cell receptor by agonist selection,” LEUKEMIA, vol. 28, no. 4, pp. 830–841, 2014.
@article{5791809,
  abstract     = {Peripheral blood T cells transduced with a tumor-specific T-cell receptor (TCR) face problems of auto-reactivity and lack of efficacy caused by cross-pairing of exogenous and endogenous TCR chains, as well as short term in vivo survival due to activation and growth factor-induced differentiation. We here studied an alternative strategy for the efficient generation of naive CD8(+) T cells with a single TCR. TCR-transduced human postnatal thymus-derived and adult mobilized blood-derived hematopoietic progenitor cells (HPCs) were differentiated to CD4(+)CD8(+) double-positive T cells using OP9-Delta-like 1 (OP9-DL1) cultures. Addition of the agonist peptide induced double positive cells to cross-present the peptide, leading, in the absence of co-stimulation, to cell cycle arrest and differentiation into mature CD8(+) T cells. comprehensive phenotypic, molecular and functional analysis revealed the generation of naive and resting CD8(+) T cells through a process similar to thymic positive selection. These mature T cells show a near complete inhibition of endogenous TCRA and TCRB rearrangements and express high levels of the introduced multimerreactive TCR. Upon activation, specific cytokine production and efficient killing of tumor cells were induced. Using this strategy, large numbers of high-avidity tumor-specific naive T cells can be generated from readily available HPCs without TCR chain cross-pairing.},
  author       = {SNAUWAERT, SYLVIA and Verstichel, Greet and Bonte, Sarah and Goetgeluk, Glenn and Vanhee, Stijn and Van Caeneghem, Yasmine and De Mulder, Katrien and Heirman, Carlo and Stauss, Hans and Heemskerk, Miriam HM and Taghon, Tom and Leclercq, Georges and Plum, Jean and Langerak, Anton W and Thielemans, Kris and Kerre, Tessa and Vandekerckhove, Bart},
  issn         = {0887-6924},
  journal      = {LEUKEMIA},
  keywords     = {antigen-specific T cell,OP9-DL1,GENE-THERAPY,STEM-CELLS,FUNCTIONAL MATURATION,PROGENITOR CELLS,HUMAN THYMOCYTES,ALPHA-BETA,EXPRESSION,LEUKEMIA,TCR,CANCER,T lymphopoiesis,hematopoietic progenitor cell,adoptive cellular immunotherapy},
  language     = {eng},
  number       = {4},
  pages        = {830--841},
  title        = {In vitro generation of mature, naive antigen-specific CD8⁺ T cells with a single T-cell receptor by agonist selection},
  url          = {http://dx.doi.org/10.1038/leu.2013.285},
  volume       = {28},
  year         = {2014},
}

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