scholarly journals Histone Deacetylase Inhibitor Modulates NKG2D Receptor Expression and Memory Phenotype of Human Gamma/Delta T Cells Upon Interaction With Tumor Cells

2019 ◽  
Vol 10 ◽  
Author(s):  
Jaydeep Bhat ◽  
Samuel Dubin ◽  
Alexandra Dananberg ◽  
Elgar Susanne Quabius ◽  
Juergen Fritsch ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Cells ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Receptor Expression ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Memory Phenotype ◽  
Deacetylase Inhibitor ◽  
Nkg2d Receptor

scholarly journals Thymus-dependent modulation of Ly49 inhibitory receptor expression on NK1.1+gamma/delta T cells

Immunology ◽  
2001 ◽  
Vol 102 (1) ◽  
pp. 24-30 ◽  
Author(s):  
T. Hara ◽  
H. Nishimura ◽  
Y. Hasegawa ◽  
Y. Yoshikai
Keyword(s):  
T Cells ◽  
Receptor Expression ◽  
Gamma Delta T Cells ◽  
Inhibitory Receptor ◽  
Gamma Delta

Human gamma delta T cells recognize heat shock protein-60 on oral tumor cells

1999 ◽  
Vol 80 (5) ◽  
pp. 709-714 ◽  
Author(s):  
Anupama D. Laad ◽  
M. Loui Thomas ◽  
Abdul R. Fakih ◽  
Shubhada V. Chiplunkar
Keyword(s):  
T Cells ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Tumor Cells ◽  
Gamma Delta T Cells ◽  
Heat Shock Protein 60 ◽  
Gamma Delta ◽  
Oral Tumor

Induction of the NKG2D Ligands Expression by Histone Deacetylase Inhibitor and Its Impact on the Susceptibility of Leukemic Cells to the Cytolytic Activity of NKG2D-Expressing Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 924-924
Author(s):  
Naoko Kato ◽  
Junji Tanaka ◽  
Junichi Sugita ◽  
Tomomi Toubai ◽  
Yoko Miura ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Histone Deacetylase ◽  
Immune Cells ◽  
Histone Deacetylase Inhibitor ◽  
Cytolytic Activity ◽  
Leukemic Cells ◽  
Expression Levels ◽  
Nkg2d Ligands ◽  
Deacetylase Inhibitor

Abstract Innate immune cells such as natural killer (NK) cells play a crucial rule in antitumor immune responses. NK cells have functionally opposite receptors for activating and inhibiting signals to exert cytotoxicity. NKG2D is a C-type lectin-like activating receptor and is expressed in various immune cells, including NK cells, NKT cells, CD8+α/β+T cells, and γ/δ+T cells. NKG2D recognizes its ligands, MHC class I-related chain A and B (MICA, MICB). NKG2D ligands are not present on normal cells but are induced by various stresses such as viral infection. Moreover NKG2D ligands are expressed in many malignant cells including hematological malignancies. It has been suggested that involvement of NKG2D in NK or CD8+Tcell-mediated cytotoxicity correlates with the expression levels of ligands on target cells. Therefore induction of NKG2D ligands may lead to enhance the sensitivity to NKG2D-mediated cytotoxicity. In this study, we could enhance expression levels of MICA and MICB by treatment with the histone deacetylase inhibitor trichostatin A (TsA) in lymphoid leukemic cell line BALL1 and some primary patients’ lymphoid leukemic cells. Treatment of BALL1 and patients’ leukemic cells with TsA for 12 hr increased MICA and MICB mRNA expression at least by more than 2 fold by Real-time PCR. Treatment of BALL1 with TsA for 12 hr increased MICA and MICB protein expression on the cell surface by more than 2 fold by flow cytometry analysis. These results suggested that expression of MICA and MICB is partly regulated by histone acetylation. Chromatin immunoprecipitation assay revealed that treatment with TsA resulted in increased acetylation of histone H3 and decreased association with the counteracting enzymes of histone acetyltransferases HDAC1 at the MICA and MICB promoter in BALL1 cell and patients’ leukemic cells. To examine the impact of the cytolytic activity of NKG2D-expressing cells on leukemic cells in which expression of NKG2D ligands was induced by TsA treatment, we performed standard 4 hr 51Cr release assays using BALL1 cells and patients’ leukemic cells. Up-regulation of NKG2D ligands by TsA treatment led to enhance the susceptibility of BALL1 and patients’ leukemic cells by 2 or 3 times to the cytolytic activity of NKG2D-expressing cells. Blocking experiment using specific antibodies for MICA and MICB inhibited the NKG2D-expressing cell-mediated cytolytic activity against BALL1 cells. Our results suggest that regulation of NKG2D ligands expression by treatment with chromatin-remodeling drugs may be an effective strategy to enhance the susceptibility of leukemic cells to the cytolytic activity of NKG2D-expressing cells for immunotherapy.

Dendritic Cells Can Be Primed to Concurrently Activate Both Unconventional Gamma/delta and Conventional alpha/beta T Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3893-3893
Author(s):  
Francesca Fiore ◽  
Barbara Castella ◽  
Barbara Nuschak ◽  
Raffaello Bertieri ◽  
Sara Mariani ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Tumor Cells ◽  
Peripheral Blood ◽  
Adoptive Cell Therapy ◽  
Effector Memory ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Alpha Beta

Abstract Vgamma9/Vdelta2 (gamma/delta) T cells represent the major subset of unconventional T cells circulating in the peripheral blood. Gamma/delta T cells play a major role in immune defenses against microbes, stressed cells and tumor cells. This property is based on their capability to naturally recognize phosphoantigens (pAgs), which are produced via the mevalonate (Mev) or the DOXP pathway in mammalian and nonmammalian cells, and induced self-ligands, which are de novo expressed or upregulated on the surface of stressed or tumor cells. Interestingly, gamma/delta T cells can also be activated by aminobisphosphonates (ABP)-treated monocytes. We have previously shown that ABP specifically target the Mev pathway of monocytes and induce the accumulation of phosphorylated Mev metabolites naturally recognized by gamma/delta T cells. The aim of this work was to determine whether ABP-treated dendritic cells (DC) can also activate gamma/delta T cells and whether this activation, if any, is detrimental or beneficial to the generation of antigen (Ag)-specific MHC-restricted immune responses mediated by conventional alpha/beta T cells. To this end, we have generated highly purified immature (iDC) and mature DC (mDC) from peripheral blood monocytes of healthy donors and incubated with zoledronic acid (Zol) for 24 hours. Zol is the most potent ABP currently available for clinical use. Zol treatment did not affect the phenotype and immunostimulatory properties of iDC and mDC. Zol-treated iDC and mDC induced a rapid and vigorous expansion of central memory and effector memory gamma/delta T cells. Zol-treated iDC were more potent inducers of gamma/delta T-cell activation than mDC and monocytes. Activated gamma/delta T cells displayed antitumor activity and expressed on the cell surface the appropriate antigen repertoire to target secondary lymphoid organs and exert costimulatory activity on conventional alpha/beta T cells. Indeed, an in vitro model showed that antigen-specific MHC-restricted immune responses againt the influenza matrix peptide were significantly improved by the concurrent activation of gamma/delta T cells. This is the first report showing that: 1) DC can simultaneously be primed to activate both gamma/delta and alpha/beta T cells; 2) the former act as cellular adjuvants for the development of adaptive immune responses. In conclusion, large numbers of gamma/delta T cells with effector and costimulatory activities can rapidly be generated by Zol-treated iDC/mDC. This strategy is worth of further investigation to improve adoptive cell therapy and vaccine interventions against tumors and infections.

The histone deacetylase inhibitor ITF2357 decreases surface CXCR4 and CCR5 expression in CD4+ T-cells and monocytes and induces latent HIV-1 expression in vitro

Cytokine ◽  
2009 ◽  
Vol 48 (1-2) ◽  
pp. 61
Author(s):  
Shay Matalon ◽  
Brent E. Palmer ◽  
Marcel F. Nold ◽  
Antonio Furlan ◽  
Gianluca Fossati ◽  
...  
Keyword(s):  
T Cells ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Cd4 T Cells ◽  
Ccr5 Expression ◽  
Deacetylase Inhibitor ◽  
Latent Hiv ◽  
Hiv 1
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