A polyadenylate binding protein localized to the granules of cytolytic lymphocytes induces DNA fragmentation in target cells

Tian, Qingsheng; Streuli, Michel; Saito, Haruo; Schlossman, Stuart F.; Anderson, Paul J.

doi:10.1016/0092-8674(91)90536-8

Cited by 353 publications

(228 citation statements)

References 41 publications

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“…49 This RNA-binding protein, lately renamed GMP-17 (granule membrane protein-17), 50 is considered a candidate effector of apoptotic cell death because of its ability to trigger DNA fragmentation of target cells. In vivo, we recently found that TIA-1 mRNA was overexpressed in melanoma metastases responding to peptide-based vaccination in humans, 29 suggesting that this molecule might be part of the tumor microenvironment gene profile that makes cancer cells responsive to immunotherapeutic manipulations.…”

Section: Il-10 and Nk Cell Activation/cytotoxicitymentioning

confidence: 99%

IL-10 stimulatory effects on human NK cells explored by gene profile analysis

et al. 2004

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The molecular mechanisms underlying the increase of natural killer (NK) cell anticancer activity mediated by interleukin (IL)-10 have not been elucidated. The aim of this study was to identify potential molecular mediators of IL-10 stimulatory effects by exploring the NK cell gene display induced by this cytokine. Gene profile was determined by high-throughput cDNA microarray and quantitative real-time PCR. In vitro, NK cells resting or conditioned with IL-10 were tested for cytotoxicity, migration and proliferation. IL-10 enhanced mRNA levels of cell activation/cytotoxicity-related genes (eg secretogranin, TIA-1, HMG-1, interferon-inducible genes) not upregulated by IL-2. In line with these findings, IL-10 increased NK cell in vitro cytotoxicity against Daudi cells. Unlike IL-2, IL-10 did not show any significant effect on NK cell in vitro proliferation and migration. However, gene profile analysis showed that IL-10 increased the expression of cell migration-related genes (eg L-selectin, vascular endothelium growth factor receptor-1, plasminogen activator, tissue; formyl peptide receptor, lipoxin A4 receptor), which might support a stimulatory effect not evident with the in vitro functional assay. Overall, gene profiling allowed us to formulate new hypotheses regarding the molecular pathways underlying the stimulatory effects of IL-10 on NK cells, supporting further investigation aimed at defining its role in cancer immune rejection.

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Section: Il-10 and Nk Cell Activation/cytotoxicitymentioning

confidence: 99%

IL-10 stimulatory effects on human NK cells explored by gene profile analysis

et al. 2004

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“…Monoclonal antibodies against TIA-1 define a subpopulation of CD8 ϩ T-cells and NK cells that have cytotoxic activity (7)(8)(9). Immunostaining using these antibodies produces a granular, cytoplasmic staining pattern in CTLs and NK cells and can be done in paraffin-embedded tissue.…”

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confidence: 99%

TIA-1 Positive Tumor-Infiltrating Lymphocytes in Nevi and Melanomas

2000

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Tumor-infiltrating lymphocytes (TIL) have been shown to be an independent prognostic factor in melanomas. To better characterize the host immune response, we have classified TIL by their immunoreactivity against lymphoid markers in formalin-fixed, paraffin-embedded tissue. Monoclonal antibodies to leukocyte common antigen (LCA) and TIA-1 (a granule-associated protein of cytotoxic T cells and NK cells) were used to immunostain a series of benign nevi, nontumorigenic radial growth phase, and tumorigenic vertical growth phase melanomas and metastases. Among nine nevi, few LCA ؉ TIL were found, among which rare cells were positive for TIA-1 (mean, 2.0). Five nontumorigenic radial growth phase melanomas also had few total TIL and rare TIA-1 ؉ TIL (mean, 3.4); the nontumorigenic radial growth phase component of seven tumorigenic vertical growth phase melanomas had higher numbers of TIA-1 ؉ TIL (mean, 11). Twelve cases of tumorigenic vertical growth phase melanoma showed a variable but significantly greater number of both LCA ؉ TIL and TIA-1 ؉ TIL (mean, 30.6). Nine cases of metastatic melanoma had a wide range of variation in LCA as well as in TIA-1 ؉ TIL (mean, 46). Although the mean total number of TIA-1 ؉ TIL increased from nontumorigenic radial growth phase to tumorigenic vertical growth phase to metastases, TIA-1 ؉ as a percentage of TIL declined across these categories of tumor progression (42%, 31%, and 26%, respectively). Our results show that these attributes of TIA-1 ؉ TIL, both increasing total number but decreasing percentage, appear to be a marker of tumor progression of malignant melanomas. In addition, there was significant variability in the number of TIA-1 ؉ TIL among advanced melanomas, raising the possibility that an assessment of TIA-1 ؉ TIL may prove a useful prognostic tool for the evaluation of primary melanomas.

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“…Activated CD8+ CTL and NK cells.hold cytotoxic granules that contain the lytic products perforin (Lichtenheld et al, 1988), granzymes: a group of highly homologous serine proteases (Jenne and Tschopp, 1988) and the Tcell-restricted intracellular antigen (Tian et al, 1991). Perforin, or pore-forming protein, causes cell lysis by generating small pores in the plasma membrane of the target cell (Lichtenheld et al, 1988).…”

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confidence: 99%

“…GrB is therefore a good marker for the identification of activated CTLs. TIA-1 is a recently identified granule-associated RNA-binding protein that may also play a role in target cell apoptosis (Tian et al, 1991). In contrast to GrB, TIA-1 is constitutively expressed in more than 50% of peripheral blood CD8+ T cells and thus may define a subpopulation of CD8+ T cells possessing cytolytic potential (Anderson, 1996).…”

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confidence: 99%