Human Vδ1 γδ T cells expanded from peripheral blood exhibit specific cytotoxicity against B-cell chronic lymphocytic leukemia-derived cells

Siegers, Gabrielle M.; Dhamko, Helena; Wang, Xinghua; Mathieson, A. Mark; Kosaka, Yoko; Felizardo, Tania C.; Medin, Jeffrey A.; Tohda, Shuji; Schueler, Julia; Fisch, Paul; Keating, Armand

doi:10.3109/14653249.2011.553595

Cited by 82 publications

(86 citation statements)

References 48 publications

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“…26, [33][34][35][36] Vd1 cells reside within epithelial tissues, especially at sites of cytomegalovirus (CMV) replication, and exert potent cytotoxic effects against acute lymphoblastic leukemia (ALL) or AML cells, 37 chronic lymphocytic leukemia cells, [38][39][40] and primary multiple myeloma cells. 41 Overall, gd T lymphocytes are important effector cells, especially in situations where the function of adaptive immunity is impaired, such as those characterizing early immune recovery after haplo-HSCT depleted of ab T cells and CD19…”

Section: Introductionmentioning

confidence: 99%

γδ T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-αβ+/CD19+ lymphocytes

Airoldi

Bertaina

Prigione

et al. 2015

Blood

218

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Section: Introductionmentioning

confidence: 99%

γδ T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-αβ+/CD19+ lymphocytes

Airoldi

Bertaina

Prigione

et al. 2015

Blood

218

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“…We also confirm a previous report (17) that C. albicans drives expansion and IL-17 production by human Vd1 T cells in vitro. We initially tested several protocols (30,31) for expanding Vd1 T cells and found that coculturing PBMCs enriched for gd T cells with DCs activated with the dectin-1 ligand curdlan in the presence of PHA and IL-2 resulted in the selective expansion of Vd1 T cells. Subsequently, it was found that substituting curdlan with heat-or ethanol-inactivated C. albicans, also known to bind dectin-1 (18)(19)(20), could similarly promote Vd1 T cell expansion in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…A number of protocols for the ex vivo expansion of human gd T cells from healthy donors were tested (30,31), and the following method was optimized for generating lines of Vd1 T cells. PBMCs prepared from buffy coat packs were enriched for total gd T cells using Ab-coated magnetic beads and cultured for 7-14 d in medium containing PHA-L and IL-2, with monocyte-derived DCs that had been matured overnight with curdlan or heat-or ethanolkilled C. albicans ( Fig.…”

Section: Albicans Drives the Expansion Of Vd1 T Cells In Vitromentioning

confidence: 99%

Candida albicansStimulates IL-23 Release by Human Dendritic Cells and Downstream IL-17 Secretion by Vδ1 T Cells

Maher

Dunne

Comerford

et al. 2015

The Journal of Immunology

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γδ T cells expressing the Vδ1 TCR are expanded in patients with HIV infection. We show in this article that circulating Vδ1 T cell numbers are particularly high in patients with HIV and candidiasis, and that these cells expand and produce IL-17 in response to Candida albicans in vitro. Although C. albicans could directly stimulate IL-17 production by a subset of Vδ1 T cells, fungus-treated dendritic cells (DCs) were required to expand C. albicans–responsive Vδ1 T cells to generate sufficient numbers of cells to release IL-17 at levels detectable by ELISA. C. albicans induced the release of IL-1β, IL-6, and IL-23 by DCs, but addition of these cytokines or supernatants of C. albicans–treated DCs to Vδ1 T cells was not sufficient to induce proliferation. We found that direct contact with DCs was required for Vδ1 T cell proliferation, whereas IL-23R–blocking studies showed that IL-23 was required for optimal C. albicans–induced IL-17 production. Because IL-17 affords protection against both HIV and C. albicans, and because Vδ1 T cells are not depleted by HIV, these cells are likely to be an important source of IL-17 in HIV-infected patients with candidiasis, in whom CD4+ Th17 responses are impaired. These data show that C. albicans stimulates proliferation and IL-17 production by Vδ1 T cells by a mechanism that involves IL-23 release by DCs.

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“…However, it is not clear whether the anti-tumor effect results primarily from the Vd1 or Vd2 T-cell subset, or both. Siegers et al 54,55 showed that fresh peripheral blood cd T cells treated with Concanavalin A and 10 ng/ml of human IL-2 and IL4 yielded higher percentages of Vd1 compared with Vd2 T cells in mixed cultures independent of day 0 subset levels in the blood. Concanavalin A exposure (leading to the apoptosis of Vd2 cells), the result demonstrates that the inhibitory effect of IL-4 can be surpassed by IL-2 stimulation, as these Vd1 cellenriched cultures were highly cytotoxic against MEC-1, a human CLL cell line, and PC-3M, a human prostate cancer cell line.…”

Section: Il-4-induced Vd1 T-cell Bias Weakened the Overall Immune Resmentioning

confidence: 99%

A new effect of IL-4 on human γδ T cells: promoting regulatory Vδ1 T cells via IL-10 production and inhibiting function of Vδ2 T cells

et al. 2015

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Interleukin 4 (IL-4) has a variety of immune functions, including helper T-cell (Th-cell) differentiation and innate immune-response processes. However, the impact of IL-4 on gamma delta (cd) T cells remains unclear. In this study, we investigate the effects of IL-4 on the activation and proliferation of cd T cells and the balance between variable delta 1 (Vd1) and Vd2 T cells in humans. The results show that IL-4 inhibits the activation of cd T cells in the presence of cd T-cell receptor (TCR) stimulation in a STAT6-dependent manner. IL-4 promoted the growth of activated cd T cells and increased the levels of Vd1 T cells, which in turn inhibited Vd2 T-cell growth via significant IL-10 secretion. Vd1 T cells secreted significantly less interferon gamma (IFNc) and more IL-10 relative to Vd2. Furthermore, Vd1 T cells showed relatively low levels of Natural Killer Group 2D (NKG2D) expression in the presence of IL-4, suggesting that Vd1 T cells weaken the cd T cell-mediated anti-tumor immune response. For the first time, our findings demonstrate a negative regulatory role of IL-4 in cd T cell-mediated anti-tumor immunity. Cellular & Molecular Immunology

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Human Vδ1 γδ T cells expanded from peripheral blood exhibit specific cytotoxicity against B-cell chronic lymphocytic leukemia-derived cells

Cited by 82 publications

References 48 publications

γδ T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-αβ+/CD19+ lymphocytes

γδ T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-αβ+/CD19+ lymphocytes

Candida albicansStimulates IL-23 Release by Human Dendritic Cells and Downstream IL-17 Secretion by Vδ1 T Cells

A new effect of IL-4 on human γδ T cells: promoting regulatory Vδ1 T cells via IL-10 production and inhibiting function of Vδ2 T cells

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