Gamma/Delta T Cells from Tolerized Alpha/Beta-TCR-Deficient Mice Antigen Specifically Inhibit Contact Sensitivity in vivo and IFN-Gamma Production in vitro

1997 ◽  
Vol 113 (1-3) ◽  
pp. 373-375 ◽  
Author(s):  
Marian Szczepanik ◽  
Laurel R. Anderson ◽  
Hiroko Ushio ◽  
Wlodzimierz Ptak ◽  
Michael J. Owen ◽  
...  
Keyword(s):  
T Cells ◽  
Gamma Delta T Cells ◽  
Contact Sensitivity ◽  
Gamma Delta ◽  
Ifn Gamma ◽  
Alpha Beta ◽  
Deficient Mice

PD-1 (CD279) Contributes to the Exhaustion of Gamma/Delta-T Cells in Tumor-Bearing Mice

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 839-839 ◽  
Author(s):  
Richard D Lopez ◽  
Shin Mineishi ◽  
Lawrence S. Lamb ◽  
Hyung-Gyoon Kim ◽  
Benjamin Beck
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Tumor Bearing ◽  
Functionally Impaired ◽  
Alpha Beta

Abstract Abstract 839 Objectives: Programmed death-1 (PD-1)/CD279 is an immunoinhibitory receptor that can be physiologically expressed on activated antigen-specific alpha/beta T-cells and is thought to play a role in maintaining a balance between T-cell activation and tolerance. Recently, both in vitro and in vivo, it has been shown that disrupting the interaction between PD-1 and its ligands can improve antitumor effects in preclinical and clinical models, this suggesting an important role played by this pathway in escape from immune surveillance. In comparison to healthy donors, gamma/delta-T cells found in tumor-bearing hosts can be diminished in number, or can be functionally impaired in a variety of important ways. While the mechanisms accounting for these numeric or functional defects have remained unclear, here we examine the extent to which PD-1 expression on gamma/delta-T cells may play a role in this process. Findings: We first noted that peripheral blood gamma/delta-T cells are diminished in numbers in patients newly diagnosed with cancer. In addition, these gamma/delta-T cells expanded poorly when cultured ex vivo. Similar to humans, in tumor-bearing mice, we found that peripheral blood gamma/delta-T cells are diminished in number and likewise, expand poorly when cultured ex vivo. Using FACS analysis of mouse peripheral blood, we first determined that a substantial proportion of gamma/delta-T cells are actively undergoing apoptosis in tumor-bearing mice compared to healthy mice. Further analysis revealed that PD-1 is significantly upregulated on gamma/delta-T cells taken from tumor-bearing mice compared to gamma/delta-T cells taken from healthy mice. In contrast, no difference of PD-1 expression was seen when comparing alpha/beta-T cells taken from tumor-bearing and healthy mice. Using in vitro co-culture studies, we next determined that apoptosis in gamma/delta-T cells can be induced by direct contact with malignant cells, but not by contact with non-malignant cells. We then showed in these cultures that PD-1 is upregulated on gamma/delta-T cells co-cultured with tumor cell lines. Moreover, we were able to determine that the PD-1-positive gamma/delta-T cells in these cultures were undergoing apoptosis to a greater extent than PD-1-negative gamma/delta-T cells in these same cultures. Finally, in vitro using CFSE-based methods, we showed that while gamma/delta-T cells isolated from healthy mice readily proliferate upon mitogen stimulation, in contrast, gamma/delta-T cells from tumor-bearing mice proliferate poorly under the same conditions. However, in spleen cell cultures derived from tumor-bearing mice, upon addition of a monoclonal antibody directed against PD-L1 (B7-H1), a ligand for PD-1, substantial restoration of gamma/delta-T cell proliferation occurs. Conclusion: Until now, the role played by PD-1 in the exhaustion of tumor-reactive gamma/delta T-cells has not been explored. Using in vitro and in vivo models, we show that the PD-1 pathway is a potentially important mechanism by which gamma/delta T-cells are either functionally impaired or otherwise exhausted in tumor-bearing mice. These findings suggest that by disrupting the PD-1 pathway, it may be possible to “revive” or “rescue” gamma/delta T-cells in tumor-bearing hosts. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Intercellular interactions and cytokine responsiveness of peritoneal alpha/beta and gamma/delta T cells from Listeria-infected mice: synergistic effects of interleukin 1 and 7 on gamma/delta T cells.

1993 ◽  
Vol 178 (3) ◽  
pp. 985-996 ◽  
Author(s):  
M J Skeen ◽  
H K Ziegler
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
T Cell Subsets ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Accessory Cells ◽  
Alpha Beta ◽  
Gamma Delta T Cell

Peritoneal gamma/delta T cells from Listeria-immune mice show an enhanced potential to expand when restimulated with antigens or mitogens in vitro (see companion paper [Skeen, M. J., and H. K. Ziegler. 1993. J. Exp. Med. 178:971]). When cocultured with peritoneal alpha/beta T cells, the gamma/delta T cell population expanded preferentially even when the in vitro stimulus was specific for the alpha/beta T cell population. Purified gamma/delta T cells did not respond to alpha/beta T cell-specific stimuli. If isolated T cell subsets were recombined in cell mixing experiments, the resulting proliferative response was greater than additive. Irradiated alpha/beta T cells could enhance the proliferation of responding gamma/delta T cells, but the effect was unidirectional; i.e., irradiated gamma/delta T cells did not stimulate responding gamma/delta T cells. This effect appeared to be cytokine mediated and did not require cell-cell contact. Both recombinant interleukin 2 (rIL-2) and rIL-7 could support the expansion of the gamma/delta T cells, while rIL-7 was only minimally stimulatory for the alpha/beta T cells. The magnitude of the response by gamma/delta T cells to rIL-7 exceeded the response to other in vitro stimuli, including immobilized anti-T cell receptor monoclonal antibody, and was 50-100-fold greater than the alpha/beta T cell response to IL-7. This unique sensitivity of gamma/delta T cells to IL-7 was strongly enhanced by the presence of accessory cells. These cells could be replaced by rIL-1, establishing a synergy for IL-1 and IL-7 as factors that could uniquely stimulate this gamma/delta T cell population. Isolated peritoneal gamma/delta T cells from Listeria-immune mice react to heat-killed Listeria preparations in the presence of macrophages accessory cells in a non-H-2-restricted manner. Considered collectively, these results suggest a potential mechanism by which gamma/delta T cells can predominate in epithelial tissues and at sites of infection.

scholarly journals A tumor-suppressor function for Fas (CD95) revealed in T cell-deficient mice.

1996 ◽  
Vol 184 (3) ◽  
pp. 1149-1154 ◽  
Author(s):  
S L Peng ◽  
M E Robert ◽  
A C Hayday ◽  
J Craft
Keyword(s):  
T Cells ◽  
Tumor Suppressor ◽  
B Cell ◽  
Malignant Tumors ◽  
B Cell Lymphoma ◽  
Immunoglobulin M ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Alpha Beta ◽  
Deficient Mice

Fas (CD95) and its ligand are central regulatory molecules in hematopoietic cells. Previous studies have suggested a role for Fas in the regulation of tumor progression, but Fas has not yet been conclusively identified as a tumor suppressor. Fas-deficient individuals lack malignant tumors, perhaps because of regulation by T cells. To investigate such a possibility, mice deficient in both T cells and Fas were generated, and they were found to develop severe B cell dysregulation characterized by malignant, lethal B cell lymphoma. Lymphoma arose from a monoclonal B220+CD19-CD5-CD23- B cell secreting immunoglobulin M, kappa rheumatoid factor. In contrast, animals containing alpha beta T cells, gamma delta T cells, and/or functional Fas suppressed the development of lymphoma. These data indicate that Fas functions as a tumor suppressor, and identifies roles for both alpha beta T cells and gamma delta T cells in Fas-independent tumor regulation.

Abstract LB148: Gamma delta T cells engineered with a chimeric PD-1 receptor effectively control PD-L1 positive tumors in vitro and in vivo with minimal toxicities

2021 ◽  
Author(s):  
Amorette Barber ◽  
Xiaohong Wang ◽  
Anupama Gopisetty ◽  
Leonardo Mirandola ◽  
Maurizio Chiriva-Internati
Keyword(s):  
T Cells ◽  
Gamma Delta T Cells ◽  
Gamma Delta

scholarly journals Gamma delta T cells contribute to immunity against the liver stages of malaria in alpha beta T-cell-deficient mice.

1994 ◽  
Vol 91 (1) ◽  
pp. 345-349 ◽  
Author(s):  
M. Tsuji ◽  
P. Mombaerts ◽  
L. Lefrancois ◽  
R. S. Nussenzweig ◽  
F. Zavala ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Alpha Beta ◽  
Deficient Mice

scholarly journals Predominant activation and expansion of V gamma 9-bearing gamma delta T cells in vivo as well as in vitro in Salmonella infection.

1992 ◽  
Vol 90 (1) ◽  
pp. 204-210 ◽  
Author(s):  
T Hara ◽  
Y Mizuno ◽  
K Takaki ◽  
H Takada ◽  
H Akeda ◽  
...  
Keyword(s):  
T Cells ◽  
Gamma Delta T Cells ◽  
Salmonella Infection ◽  
Gamma Delta

600 In vitro anticancer and immunomodulatory activities of NBT-167, a dimer of resveratrol

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A635-A635
Author(s):  
Jeffrey Zhang ◽  
Everett Henry ◽  
L Harris Zhang ◽  
Wanying Zhang
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Immune Cells ◽  
Cell Killing ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Raw264.7 Macrophages

BackgroundResveratrol (3,4’,5-trihydroxystilbene), a stilbenoid isolated from many species of plants, is widely known for its antioxidative, anti-inflammatory, immunomodulatory and anticancer activities. Recently, novel resveratrol oligomers have been isolated from various plants; their diverse structures are characterized by the polymerization of two or more resveratrol units. Little is known regarding the anticancer and immunomodulating activities of these oligomers. In this study, we designed in vitro models to compare resveratrol side by side with its natural dimer NBT-167 for their anticancer and immunological activities.MethodsWe isolated resveratrol and its dimer (NBT-167) from plants. The potency of the compounds was compared side by side using cancer cell survival assays and immunological assays with various types of human cells including cancer cell lines, PBMCs and enriched NK, gamma delta T cells, THP-1 monocytic cells, HL-60 promyelocytic leukemia cells as well as mouse RAW264.7 macrophages.ResultsNBT-167 was found to be more potent than resveratrol in inhibiting growth of various cancer cells and modulation of cytokine production from anti-IgM, LPS, PHA or SEB stimulated PBMC. Both compounds similarly enhanced IL-2 stimulated NK and gamma delta T cell killing activity against K562 cells and modulated nitric oxide production from LPS/IFN-g induced RAW264.7 macrophages and phagocytotic activity of HL-60 cells. NBT-167 was slightly more potently than resveratrol in inhibiting chemotaxis of HL-60 cells and blocking cell cycle of THP-1 and HL-60 cells at G1/S transition. In addition, NBT-167, but not resveratrol, could increase IL-2 production and T cell proliferation stimulated with anti-CD3 and anti-CD28 and synergize with anti-PD-1 antibody to increase IL-2 and IFN-gamma production in co-culture of allotypic T cells and dendric cells (MLR).ConclusionsOur data showed that NBT-167, a dimer of resveratrol, had anticancer and immunomodulatory activities such as modulation of expression of cytokines in immune cells and induction of cancer cell-killing activities of NK and gamma delta T cells. Generally, NBT-167 appeared to have higher activities than resveratrol in modulating immune cells and inhibiting cancer cells. NBT-167 could be a promising cancer immunotherapeutic agent targeting both cancer cells and immune cells.

Sign in / Sign up

Export Citation Format

Share Document