Regulatory Role of CD8 in Major Histocompatibility Complex-Unrestricted Tumoricidal Activity of Mouse T Cells Activated with Anti-CD3 Monoclonal Antibody

Bh, Stewart; Dw, Hoskin

doi:10.3109/08820139709088544

Cited by 6 publications

(4 citation statements)

References 34 publications

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“…To account for nonspecific, OVA-independent, cytolytic activity in the expanded splenic lymphocyte population, we also conducted control assays using B16-F10 melanoma cells that do not express ovalbumin. As previously reported (18)(19)(20), there was some nonspecific cytolytic activity of CD3…”

Section: Resultssupporting

confidence: 64%

A Mechanism of Hypoxia-Mediated Escape from Adaptive Immunity in Cancer Cells

et al. 2014

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Immune escape is a fundamental trait of cancer in which mechanistic knowledge is incomplete. Here, we describe a novel mechanism by which hypoxia contributes to tumoral immune escape from cytotoxic T lymphocytes (CTL). Exposure of human or murine cancer cells to hypoxia for 24 hours led to upregulation of the immune inhibitory molecule programmed cell death ligand-1 (PD-L1; also known as B7-H1), in a manner dependent on the transcription factor hypoxia-inducible factor-1a (HIF-1a). In vivo studies also demonstrated cellular colocalization of HIF-1a and PD-L1 in tumors. Hypoxia-induced expression of PD-L1 in cancer cells increased their resistance to CTL-mediated lysis. Using glyceryl trinitrate (GTN), an agonist of nitric oxide (NO) signaling known to block HIF-1a accumulation in hypoxic cells, we prevented hypoxiainduced PD-L1 expression and diminished resistance to CTL-mediated lysis. Moreover, transdermal administration of GTN attenuated tumor growth in mice. We found that higher expression of PD-L1 induced in tumor cells by exposure to hypoxia led to increased apoptosis of cocultured CTLs and Jurkat leukemia T cells. This increase in apoptosis was prevented by blocking the interaction of PD-L1 with PD-1, the PD-L1 receptor on T cells, or by addition of GTN. Our findings point to a role for hypoxia/HIF-1 in driving immune escape from CTL, and they suggest a novel cancer immunotherapy to block PD-L1 expression in hypoxic-tumor cells by administering NO mimetics. Cancer Res; 74(3); 665-74. Ó2013 AACR.

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Section: Resultssupporting

confidence: 64%

A Mechanism of Hypoxia-Mediated Escape from Adaptive Immunity in Cancer Cells

et al. 2014

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“…Mouse lymphoma YAC-1 cells (Japanese Collection of Research Bioresources) were maintained in Roswell Park Memorial Institute-1640 (RPMI) medium (Sigma) supplemented with 10 % (v/v) fetal bovine serum (Nippon Biotest), 5 m m -HEPES (Sigma), 1 % penicillin–streptomycin solution (p4458; Sigma) and 100 μg streptomycin/ml (Sigma) (complete RPMI-1640 medium). NK cells ( 17 ) , CD8 + cytotoxic T cells ( 18 ) and macrophages ( 19 ) showed cytotoxicity against the cells.…”

Section: Methodsmentioning

confidence: 99%

Effect ofLactobacillus brevisKB290 on the cell-mediated cytotoxic activity of mouse splenocytes: a DNA microarray analysis

Fukui¹,

Sasaki²,

Fuke³

et al. 2013

Br J Nutr

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Lactic acid bacteria confer a variety of health benefits. Here, we investigate the mechanisms by which Lactobacillus brevis KB290 (KB290) enhances cell-mediated cytotoxic activity. Female BALB/c mice aged 9 weeks were fed a diet containing KB290 (3 £ 10 9 colony-forming units/g) or starch for 1 d. The resulting cytotoxic activity of splenocytes against YAC-1 cells was measured using flow cytometry and analysed for gene expression using DNA microarray technology. KB290 enhanced the cell-mediated cytotoxic activity of splenocytes. DNA microarray analysis identified 327 up-regulated and 347 down-regulated genes that characterised the KB290 diet group. The up-regulated genes were significantly enriched in Gene Ontology terms related to immunity, and, especially, a positive regulation of T-cell-mediated cytotoxicity existed among these terms. Almost all the genes included in the term encoded major histocompatibility complex (MHC) class I molecules involved in the presentation of antigen to CD8 þ cytotoxic T cells. Marco and Signr1 specific to marginal zone macrophages (MZM), antigen-presenting cells, were also up-regulated. Flow cytometric analysis confirmed that the proportion of MZM was significantly increased by KB290 ingestion. Additionally, the over-represented Kyoto Encyclopedia of Genes and Genomes pathways among the up-regulated genes were those for natural killer (NK) cell-mediated cytotoxicity and antigen processing and presentation. The results for the selected genes associated with NK cells and CD8 þ cytotoxic T cells were confirmed by quantitative RT-PCR. These results suggest that enhanced cytotoxic activity could be caused by the activation of NK cells and/or of CD8 þ cytotoxic T cells stimulated via MHC class I presentation.

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“…AsGm‐1 depletion also depletes NK and CD8 cells thus decreasing net cytotoxic activity (14). CD8 cells have been shown to be associated in inflammatory bowel disease and to be cytotoxic towards YAC‐1 cells (64,65). Depletion of AsGm‐1 expressing cells may have decreased the cytotoxicity levels as both CD8 and NK were depleted.…”

Section: Discussionmentioning

confidence: 99%

Role of NK1.1+ and AsGm-1+ Cells in Oral Immunoregulation of Experimental Colitis

Trop¹,

Nagler

Ilan³

2003

Inflammatory Bowel Diseases

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NK1.1 and AsGm-1 expressing cells play a role in immunomodulation. Our purpose was to determine the role of NK1.1+ and AsGm-1+ expressing cells in the inflammatory/tolerance paradigm in experimental colitis. Oral tolerance towards colitis-extracted proteins had previously been shown to alleviate experimental colitis. Colitis was induced in C57/B6 mice by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS). Oral tolerance was induced via five oral doses of proteins extracted from TNBS-colitis colonic wall. Clinical, macroscopic, and microscopic scores were used for colitis assessment. To evaluate the putative role of AsGm-1 in tolerance induction, depletion of AsGm-1 expressing cells was performed. To evaluate the mechanism of tolerance induction, liver-associated NKT lymphocytes were harvested 14 days following tolerance induction, and cultured with concanavalin A (con A) and colitis-extracted proteins. T cell subsets were measured by flow cytometry. Cytokine expression was measured by intracellular staining and enzyme-linked immunosorbent assay (ELISA). Orally tolerized mice exhibited significant alleviation of the clinical, macroscopic, and microscopic parameters of colitis, with increased CD4+ILA+/CD4+IFNgamma+ lymphocyte ratio, increased IL-4, and decreased IFNgamma and IL-12 serum levels. In contrast, orally fed mice that were AsGm-1 depleted showed evidence of severe colitis. These mice exhibited significant decreased CD4 +IL4+/CD4+IFNgamma+ ratios, and an increase in IFNgamma and IL-12, with decreased IL-4 levels. NKT cells harvested from tolerized mice secreted high levels of antiinflammatory cytokines. In contrast, in nontolerized mice, NKT cells mainly secreted proinflammatory cytokines. In a tolerized environment, both NK1.1 and AsGm-1 expressing cells are essential for disease alleviation. In contrast, in a nontolerized environment, AsGm-1 expressing cells support an antiinflammatory immune paradigm, while NKT lymphocytes support a proinflammatory shift.

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Regulatory Role of CD8 in Major Histocompatibility Complex-Unrestricted Tumoricidal Activity of Mouse T Cells Activated with Anti-CD3 Monoclonal Antibody

Cited by 6 publications

References 34 publications

A Mechanism of Hypoxia-Mediated Escape from Adaptive Immunity in Cancer Cells

A Mechanism of Hypoxia-Mediated Escape from Adaptive Immunity in Cancer Cells

Effect ofLactobacillus brevisKB290 on the cell-mediated cytotoxic activity of mouse splenocytes: a DNA microarray analysis

Role of NK1.1+ and AsGm-1+ Cells in Oral Immunoregulation of Experimental Colitis

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