Differential expression of the granzymes A, K and M and perforin in human peripheral blood lymphocytes

Bade, Britta; Boettcher, H; Lohrmann, Jens; Hink-Schauer, Clara; Bratke, Kai; Jenne, Dieter E.; Virchow, J. Christian; Luttmann, Werner

doi:10.1093/intimm/dxh320

Cited by 81 publications

(70 citation statements)

References 45 publications

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“…Furthermore, granzyme-deficient mice have also shown abnormalities of the CD8 T-cell cytotoxic function and association with various degrees of immunodeficiency (19). A series of studies has previously investigated the profiles of cytotoxic-granule distribution in human CD8 T cells, and some patterns of cytotoxic-granule distribution have been shown to preferentially associate with certain stages of differentiation and cytotoxic activity (2,5,12,16,23,35,50,61).…”

Section: Discussionmentioning

confidence: 99%

Distinct Profiles of Cytotoxic Granules in Memory CD8 T Cells Correlate with Function, Differentiation Stage, and Antigen Exposure

Harari

Enders

Cellerai

et al. 2009

J Virol

108

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Cytotoxic CD8 T cells exert their antiviral and antitumor activity primarily through the secretion of cytotoxic granules. Degranulation activity and cytotoxic granules (perforin plus granzymes) generally define CD8 T cells with cytotoxic function. In this study, we have investigated the expression of granzyme K (GrmK) in comparison to that of GrmA, GrmB, and perforin. The expression of the cytotoxic granules was assessed in virusspecific CD8 T cells specific to influenza virus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), or human immunodeficiency virus type 1 (HIV-1). We observed a dichotomy between GrmK and perforin expression in virus-specific CD8 T cells. The profile in influenza virus-specific CD8 T cells was perforin

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Section: Discussionmentioning

confidence: 99%

Distinct Profiles of Cytotoxic Granules in Memory CD8 T Cells Correlate with Function, Differentiation Stage, and Antigen Exposure

Harari

Enders

Cellerai

et al. 2009

J Virol

108

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“…In adenovirus-infected cells, it cleaves the adenovirus DNA-binding protein, which is required for viral DNA replication (35). In humans, GzmK is expressed in NK cells, in a subset of CD4 + T-cells, and in a subpopulation of memory CD8 + T-cells (21,36). When delivered into cells, GzmK induces a caspaseindependent apoptosis, with processing of Bid by GzmK itself, and release of cytochrome c from mitochondria (37).…”

Section: Discussionmentioning

confidence: 99%

Functions of Anti-MAGE T-Cells Induced in Melanoma Patients under Different Vaccination Modalities

Connerotte

Pel²,

Godelaine³

et al. 2008

Cancer Research

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Tumor regressions have been observed in a small proportion of melanoma patients vaccinated with a MAGE-A3 peptide presented by HLA-A1, administered as peptide, ALVAC canarypox virus containing a MAGE-A3 minigene, or peptide-pulsed dendritic cells (DC). There was a correlation between tumor regression and the detection of anti-MAGE-3.A1 CTL responses. These responses were monoclonal and often of a very low magnitude after vaccination with peptide or ALVAC, and usually polyclonal and of a higher magnitude after DC vaccination. These results suggested that, at least in some patients, surprisingly few anti-MAGE-3.A1 T-cells could initiate a tumor regression process. To understand the role of these T cells, we carried out a functional analysis of anti-MAGE-3.A1 CTL clones derived from vaccinated patients who displayed tumor regression. The functional avidities of these CTL clones, evaluated in lysis assays, were surprisingly low, suggesting that high avidity was not part of the putative capability of these CTL to trigger tumor rejection. Most anti-MAGE-3.A1 CTL clones obtained after DC vaccination, but not after peptide or ALVAC vaccination, produced interleukin 10. Transcript profiling confirmed these results and indicated that approximately 20 genes, including CD40L, prostaglandin D2 synthase, granzyme K, and granzyme H, were highly differentially expressed between the anti-MAGE-3.A1 CTL clones derived from patients vaccinated with either peptide-ALVAC or peptide-pulsed DC. These results indicate that the modality of vaccination with a tumor-specific antigen influences the differentiation pathway of the antivaccine CD8 T-cells, which may have an effect on their capacity to trigger a tumor rejection response. [Cancer Res 2008;68(10):3931-40]

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“…For indirect IC staining, mouse monoclonal IgG1 Abs were used: anti-GNLY (RB1, MBL International, Woburn, MA), anti-granzyme K, and anti-granzyme M (gift from J. Lohrmann and B. Bade, GENOVAC, Freiburg, Germany) (28). After washing and a 10-min blocking step with goat serum, cells were incubated with a goat FITC-anti-mouse IgG1 secondary Ab (Southern Biotechnology Associates) for 20 min.…”

Section: Flow Cytometrymentioning

confidence: 99%

Human Eosinophils Exert TNF-α and Granzyme A-Mediated Tumoricidal Activity toward Colon Carcinoma Cells

Legrand

Driss

Delbeke

et al. 2010

The Journal of Immunology

144

135

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Peripheral blood and tissue eosinophilia is a prominent feature in allergic diseases and helminth infections. In cancer patients, tumor-associated tissue eosinophilia is frequently observed. Tumor-associated tissue eosinophilia can be associated with a favorable prognosis, notably in colorectal carcinoma. However, underlying mechanisms of eosinophil contribution to antitumor responses are poorly understood. We have in this study investigated the direct interactions of human eosinophils with Colo-205, a colorectal carcinoma cell line, and show that eosinophils induce apoptosis and directly kill tumor cells. Using blocking Abs, we found that CD11a/CD18 complex is involved in the tumoricidal activity. Coculture of eosinophils with Colo-205 led to the release of eosinophil cationic protein and eosinophil-derived neurotoxin as well as TNF-α secretion. Moreover, eosinophils expressed granzyme A, which was released upon interaction with Colo-205, whereas cytotoxicity was partially inhibited by FUT-175, an inhibitor of trypsin-like enzymatic activity. Our data present the first demonstration, to our knowledge, that granzyme A is a cytotoxic mediator of the eosinophil protein arsenal, exerting eosinophil tumoricidal activity toward Colo-205, and provide mechanistic evidence for innate responses of eosinophil against tumor cells.

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Differential expression of the granzymes A, K and M and perforin in human peripheral blood lymphocytes

Cited by 81 publications

References 45 publications

Distinct Profiles of Cytotoxic Granules in Memory CD8 T Cells Correlate with Function, Differentiation Stage, and Antigen Exposure

Distinct Profiles of Cytotoxic Granules in Memory CD8 T Cells Correlate with Function, Differentiation Stage, and Antigen Exposure

Functions of Anti-MAGE T-Cells Induced in Melanoma Patients under Different Vaccination Modalities

Human Eosinophils Exert TNF-α and Granzyme A-Mediated Tumoricidal Activity toward Colon Carcinoma Cells

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