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Anti-leukemia activity of human gamma delta T cells.

Siegers GM - Oncoimmunology (2012)

Bottom Line: Two recently published articles from Siegers and colleagues detail both a novel human gamma delta T cell (GDTc) expansion protocol and a bioluminescent xenograft model of Ph(+) leukemia, in which GDTc adoptive therapy was tested.Additionally, B-cell chronic lymphocytic leukemia-derived cells were newly identified as targets of preferentially expanded Vdelta1 GDTc.

View Article: PubMed Central - PubMed

ABSTRACT
Two recently published articles from Siegers and colleagues detail both a novel human gamma delta T cell (GDTc) expansion protocol and a bioluminescent xenograft model of Ph(+) leukemia, in which GDTc adoptive therapy was tested. Additionally, B-cell chronic lymphocytic leukemia-derived cells were newly identified as targets of preferentially expanded Vdelta1 GDTc.

No MeSH data available.


Related in: MedlinePlus

Figure 1. (A) Gamma delta T cells (GDTc) isolated from human blood were cultured for six to eight days in complete medium containing Concanavalin A (ConA). Vdelta1 (Vδ1) or Vdelta2 (Vδ2) subset prevalence in expanded culture correlated with the duration of exposure to ConA. (B) Vδ2 GDTc are cytotoxic to EM-2eGFPluc cells, Ph+ leukemia cells transduced with a lentiviral vector encoding eGFP and luciferase. Both Vδ1 and Vδ2 are cytotoxic to B-CLL-derived MEC1 and TMD2 cell lines. (C) The bioluminescent xenograft Ph+ leukemia model was established via intravenous (IV) injection of EM-2eGFPluc cells. Vδ2 GDTc therapy was investigated; infusion of GDTc intraperitoneally gave rise to better engraftment than when GDTc were injected IV. (D) Leukemia progression was monitored in vivo via IVIS® technology (In Vivo Imaging System, Xenogen). Shown here are representative examples of treated and leukemia-bearing mice. Red circles are regions of interest from which bioluminescence values were quantified.
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Figure 1: Figure 1. (A) Gamma delta T cells (GDTc) isolated from human blood were cultured for six to eight days in complete medium containing Concanavalin A (ConA). Vdelta1 (Vδ1) or Vdelta2 (Vδ2) subset prevalence in expanded culture correlated with the duration of exposure to ConA. (B) Vδ2 GDTc are cytotoxic to EM-2eGFPluc cells, Ph+ leukemia cells transduced with a lentiviral vector encoding eGFP and luciferase. Both Vδ1 and Vδ2 are cytotoxic to B-CLL-derived MEC1 and TMD2 cell lines. (C) The bioluminescent xenograft Ph+ leukemia model was established via intravenous (IV) injection of EM-2eGFPluc cells. Vδ2 GDTc therapy was investigated; infusion of GDTc intraperitoneally gave rise to better engraftment than when GDTc were injected IV. (D) Leukemia progression was monitored in vivo via IVIS® technology (In Vivo Imaging System, Xenogen). Shown here are representative examples of treated and leukemia-bearing mice. Red circles are regions of interest from which bioluminescence values were quantified.

Mentions: Our GDTc expansion protocol expands both Vgamma9Vdelta2 GDTc (Vδ2) and also the lesser-prevalent Vdelta1 GDTc (Vδ1) subset from human blood.6 A correlation between duration of initial GDTc exposure to Concanavalin A (ConA) and expansion of Vδ1 was evident (Fig. 1A). Bartkowiak and colleagues reported an expanded population of Vδ1 in the blood of B-CLL patients.8 Thus, using mixed Vδ1/Vδ2 cultures, the CD107 mobilization assay9 was employed to simultaneously test activation of GDTc subsets against Philadelphia chromosome positive (Ph+) or B-cell chronic lymphocytic leukemia (B-CLL)-derived cells. Indeed, this approach could be applied to any target of interest. While Ph+ EM2 cells only activated Vδ2, both Vδ1 and Vδ2 were activated by B-CLL-derived MEC1 and TMD2 (Fig. 1B), thus obviating the need to separate subsets for possible future autologous cellular therapy of B-CLL. An interesting line of study made uniquely possible by generation of mixed cultures is the influence exerted by one GDTc subset on the other; for example, one could explore whether Vδ2 activation suppresses Vδ1.


Anti-leukemia activity of human gamma delta T cells.

Siegers GM - Oncoimmunology (2012)

Figure 1. (A) Gamma delta T cells (GDTc) isolated from human blood were cultured for six to eight days in complete medium containing Concanavalin A (ConA). Vdelta1 (Vδ1) or Vdelta2 (Vδ2) subset prevalence in expanded culture correlated with the duration of exposure to ConA. (B) Vδ2 GDTc are cytotoxic to EM-2eGFPluc cells, Ph+ leukemia cells transduced with a lentiviral vector encoding eGFP and luciferase. Both Vδ1 and Vδ2 are cytotoxic to B-CLL-derived MEC1 and TMD2 cell lines. (C) The bioluminescent xenograft Ph+ leukemia model was established via intravenous (IV) injection of EM-2eGFPluc cells. Vδ2 GDTc therapy was investigated; infusion of GDTc intraperitoneally gave rise to better engraftment than when GDTc were injected IV. (D) Leukemia progression was monitored in vivo via IVIS® technology (In Vivo Imaging System, Xenogen). Shown here are representative examples of treated and leukemia-bearing mice. Red circles are regions of interest from which bioluminescence values were quantified.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376996&req=5

Figure 1: Figure 1. (A) Gamma delta T cells (GDTc) isolated from human blood were cultured for six to eight days in complete medium containing Concanavalin A (ConA). Vdelta1 (Vδ1) or Vdelta2 (Vδ2) subset prevalence in expanded culture correlated with the duration of exposure to ConA. (B) Vδ2 GDTc are cytotoxic to EM-2eGFPluc cells, Ph+ leukemia cells transduced with a lentiviral vector encoding eGFP and luciferase. Both Vδ1 and Vδ2 are cytotoxic to B-CLL-derived MEC1 and TMD2 cell lines. (C) The bioluminescent xenograft Ph+ leukemia model was established via intravenous (IV) injection of EM-2eGFPluc cells. Vδ2 GDTc therapy was investigated; infusion of GDTc intraperitoneally gave rise to better engraftment than when GDTc were injected IV. (D) Leukemia progression was monitored in vivo via IVIS® technology (In Vivo Imaging System, Xenogen). Shown here are representative examples of treated and leukemia-bearing mice. Red circles are regions of interest from which bioluminescence values were quantified.
Mentions: Our GDTc expansion protocol expands both Vgamma9Vdelta2 GDTc (Vδ2) and also the lesser-prevalent Vdelta1 GDTc (Vδ1) subset from human blood.6 A correlation between duration of initial GDTc exposure to Concanavalin A (ConA) and expansion of Vδ1 was evident (Fig. 1A). Bartkowiak and colleagues reported an expanded population of Vδ1 in the blood of B-CLL patients.8 Thus, using mixed Vδ1/Vδ2 cultures, the CD107 mobilization assay9 was employed to simultaneously test activation of GDTc subsets against Philadelphia chromosome positive (Ph+) or B-cell chronic lymphocytic leukemia (B-CLL)-derived cells. Indeed, this approach could be applied to any target of interest. While Ph+ EM2 cells only activated Vδ2, both Vδ1 and Vδ2 were activated by B-CLL-derived MEC1 and TMD2 (Fig. 1B), thus obviating the need to separate subsets for possible future autologous cellular therapy of B-CLL. An interesting line of study made uniquely possible by generation of mixed cultures is the influence exerted by one GDTc subset on the other; for example, one could explore whether Vδ2 activation suppresses Vδ1.

Bottom Line: Two recently published articles from Siegers and colleagues detail both a novel human gamma delta T cell (GDTc) expansion protocol and a bioluminescent xenograft model of Ph(+) leukemia, in which GDTc adoptive therapy was tested.Additionally, B-cell chronic lymphocytic leukemia-derived cells were newly identified as targets of preferentially expanded Vdelta1 GDTc.

View Article: PubMed Central - PubMed

ABSTRACT
Two recently published articles from Siegers and colleagues detail both a novel human gamma delta T cell (GDTc) expansion protocol and a bioluminescent xenograft model of Ph(+) leukemia, in which GDTc adoptive therapy was tested. Additionally, B-cell chronic lymphocytic leukemia-derived cells were newly identified as targets of preferentially expanded Vdelta1 GDTc.

No MeSH data available.


Related in: MedlinePlus