Giorgia Gri's Publications List

Exacerbated experimental autoimmune encephalomyelitis in mast-cell-deficient Kit W-sh/W-sh mice.

2011-06-13T12:45:36Z

Mast cell (MC)-deficient c-Kit mutant Kit(W/W-v) mice are protected against experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, suggesting a detrimental role for MCs in this disease. To further investigate the role of MCs in EAE, we took advantage of a recently characterized model of MC deficiency, Kit(W-sh/W-sh). Surprisingly, we observed that myelin oligodendr...

Silvia Piconese, Massimo Costanza, Silvia Musio, Claudio Tripodo, Pietro L Poliani, Giorgia Gri, Alessia Burocchi, Paola Pittoni, Andrea Gorzanelli, Mario P Colombo, Rosetta Pedotti (2011) Lab Invest 91: 4 627-641

Single-cell dynamics of mast cell-CD4(+) CD25(+) regulatory T cell interactions.

2011-06-13T12:45:36Z

The biological behavior of immune cells is determined by their intrinsic properties and interactions with other cell populations within their microenvironment. Several studies have confirmed the existence of tight spatial interactions between mast cells (MCs) and Tregs in different settings. For instance, we have recently identified the functional cross-talk between MCs and Tregs, through the OX40...

Barbara Frossi, Federica D'Incà, Enrico Crivellato, Riccardo Sibilano, Giorgia Gri, Marco Mongillo, Luca Danelli, Laura Maggi, Carlo E Pucillo (2011) Eur J Immunol :

Technical Advance:Soluble OX40 molecule mimics regulatory T cell modulatory activity on Fc{varepsilon}RI-dependent mast cell degranulation.

2011-06-13T12:45:36Z

Tregs play a central role in modulating FcεRI-dependent MC effector functions in the course of the allergic response. Cellular interaction depends on the constitutive expression of OX40 on Tregs and the OX40L counterpart on MCs. Study of OX40L signaling on MCs is hampered by the need of a highly purified molecule, which triggers OX40L specifically. We now report that sOX40 mimics the physiologica...

Riccardo Sibilano, Giorgia Gri, Barbara Frossi, Claudio Tripodo, Ryo Suzuki, Juan Rivera, Andrew S Macdonald, Carlo E Pucillo (2011) J Leukoc Biol :

Exploring a regulatory role for mast cells: 'MCregs'?

2011-06-13T12:45:36Z

Regulatory cells can mould the fate of the immune response by direct suppression of specific subsets of effector cells, or by redirecting effectors against invading pathogens and infected or neoplastic cells. These functions have been classically, although not exclusively, ascribed to different subsets of T cells. Recently, mast cells have been shown to regulate physiological and pathological immu...

Barbara Frossi, Giorgia Gri, Claudio Tripodo, Carlo Pucillo (2010) Trends Immunol 31: 3 97-102

Mast cells and Th17 cells contribute to the lymphoma-associated pro-inflammatory microenvironment of angioimmunoblastic T-cell lymphoma.

2011-06-13T12:45:36Z

Reports focusing on the immunological microenvironment of peripheral T-cell lymphomas (PTCL) are rare. Here we studied the reciprocal contribution of regulatory (Treg) and interleukin-17-producing (Th17) T-cells to the composition of the lymphoma-associated microenvironment of angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified on tissue microarrays from 30 PTCLs not otherwi...

Claudio Tripodo, Giorgia Gri, Pier Paolo Piccaluga, Barbara Frossi, Carla Guarnotta, Silvia Piconese, Giovanni Franco, Valeria Vetri, Carlo Ennio Pucillo, Ada Maria Florena, Mario Paolo Colombo, Stefano Aldo Pileri (2010) Am J Pathol 177: 2 792-802

Mast cells enhance proliferation of B lymphocytes and drive their differentiation toward IgA-secreting plasma cells.

2011-06-13T12:45:36Z

The evidence of a tight spatial interaction between mast cells (MCs) and B lymphocytes in secondary lymphoid organs, along with the data regarding the abundance of MCs in several B-cell lymphoproliferative disorders prompted us to investigate whether MCs could affect the proliferation and differentiation of B cells. To this aim, we performed coculture assays using mouse splenic B cells and bone ma...

Sonia Merluzzi, Barbara Frossi, Giorgia Gri, Serena Parusso, Claudio Tripodo, Carlo Pucillo (2010) Blood 115: 14 2810-2817

Mast cells counteract regulatory T-cell suppression through interleukin-6 and OX40/OX40L axis toward Th17-cell differentiation.

2011-06-13T12:45:36Z

The development of inflammatory diseases implies inactivation of regulatory T (Treg) cells through mechanisms that still are largely unknown. Here we showed that mast cells (MCs), an early source of inflammatory mediators, are able to counteract Treg inhibition over effector T cells. To gain insight into the molecules involved in their interplay, we set up an in vitro system in which all 3 cellula...

Silvia Piconese, Giorgia Gri, Claudio Tripodo, Silvia Musio, Andrea Gorzanelli, Barbara Frossi, Rosetta Pedotti, Carlo E Pucillo, Mario P Colombo (2009) Blood 114: 13 2639-2648

CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction.

2011-06-13T12:45:36Z

T regulatory (Treg) cells play a role in the suppression of immune responses, thus serving to induce tolerance and control autoimmunity. Here, we explored whether Treg cells influence the immediate hypersensitivity response of mast cells (MCs). Treg cells directly inhibited the FcvarepsilonRI-dependent MC degranulation through cell-cell contact involving OX40-OX40L interactions between Treg cells ...

Giorgia Gri, Silvia Piconese, Barbara Frossi, Vanessa Manfroi, Sonia Merluzzi, Claudio Tripodo, Antonella Viola, Sandra Odom, Juan Rivera, Mario P Colombo, Carlo E Pucillo (2008) Immunity 29: 5 771-781

APE/Ref-1 makes fine-tuning of CD40-induced B cell proliferation.

2011-06-13T12:45:36Z

Apurinic/apyrimidinic endonuclease-1/Redox factor-1, a multifunctional DNA base excision repair and redox regulation enzyme, plays an important role in oxidative signalling, transcription factor regulation, and cell cycle control. Recently, we have demonstrated that following the triggering of CD40 on B cells, APE/Ref-1 translocates from the cytoplasm to the nucleus and regulates the activity of B...

Sonia Merluzzi, Giorgia Gri, Valter Gattei, Michele Pagano, Carlo Pucillo (2008) Mol Immunol 45: 14 3731-3739

Outside inside signalling in CD40-mediated B cell activation.

2011-06-13T12:45:36Z

CD40 is a member of the growing tumor necrosis factor receptor (TNF-R) family of molecules, and has been shown to play important roles in T cell-mediated B lymphocyte activation. Ligation of B cell CD40 by CD154 expressed on activated T cells stimulates B cell proliferation, differentiation, isotype switching, upregulation of surface molecules contributing to antigen presentation, development of t...

O D'Orlando, G Gri, G Cattaruzzi, S Merluzzi, E Betto, V Gattei, C Pucillo (2007) J Biol Regul Homeost Agents 21: 3-4 49-62

Boosting antitumor responses of T lymphocytes infiltrating human prostate cancers.

2011-06-13T12:48:00Z

Immunotherapy may provide valid alternative therapy for patients with hormone-refractory metastatic prostate cancer. However, if the tumor environment exerts a suppressive action on antigen-specific tumor-infiltrating lymphocytes (TIL), immunotherapy will achieve little, if any, success. In this study, we analyzed the modulation of TIL responses by the tumor environment using collagen gel matrix-s...

Vincenzo Bronte, Tihana Kasic, Giorgia Gri, Keti Gallana, Giovanna Borsellino, Ilaria Marigo, Luca Battistini, Massimo Iafrate, Tommaso Prayer-Galetti, Francesco Pagano, Antonella Viola (2005) J Exp Med 201: 8 1257-1268

T cell costimulation by chemokine receptors.

2011-06-13T12:48:00Z

Signals mediated by chemokine receptors may compete with T cell receptor stop signals and determine the duration of T cell-antigen-presenting cell interactions. Here we show that during T cell stimulation by antigen-presenting cells, T cell chemokine receptors coupled to G(q) and/or G(11) protein were recruited to the immunological synapse by a G(i)-independent mechanism. When chemokine receptors ...

Barbara Molon, Giorgia Gri, Monica Bettella, Concepción Gómez-Moutón, Antonio Lanzavecchia, Carlos Martínez-A, Santos Mañes, Antonella Viola (2005) Nat Immunol 6: 5 465-471

The inner side of T cell lipid rafts.

2011-06-13T12:48:00Z

A key question in understanding the functional role of lipid rafts is whether lipid microdomains at the plasma membrane outer leaflet are coupled to lipid microdomains at the inner leaflet. By using a cyan-fluorescent protein (CFP) targeted to inner plasma membrane rafts of Jurkat T cells, we found that raft domains at the outer and inner leaflets are physically coupled and that this coupling requ...

Giorgia Gri, Barbara Molon, Santos Manes, Tullio Pozzan, Antonella Viola (2004) Immunol Lett 94: 3 247-252

CD28 and lipid rafts coordinate recruitment of Lck to the immunological synapse of human T lymphocytes.

2011-06-13T12:48:00Z

In T lymphocytes, the Src family kinase Lck associates lipid rafts and accumulates at the immunological synapse (IS) during T cell stimulation by APCs. Using CD4- or CD28-deficient murine T cells, it was suggested that recruitment of Lck to the IS depends on CD4, whereas CD28 sustains Lck activation. However, in human resting T cells, CD28 is responsible for promoting recruitment of lipid rafts to...

Regina Tavano, Giorgia Gri, Barbara Molon, Barbara Marinari, Christopher E Rudd, Loretta Tuosto, Antonella Viola (2004) J Immunol 173: 9 5392-5397

OX40 ligand-transduced tumor cell vaccine synergizes with GM-CSF and requires CD40-Apc signaling to boost the host T cell antitumor response.

2011-06-13T12:48:00Z

Efficient T cell priming by GM-CSF and CD40 ligand double-transduced C26 murine colon carcinoma is not sufficient to cure metastases in a therapeutic setting. To determine whether a cellular vaccine that interacts directly with both APC and T cells in vivo might be superior, we generated C26 carcinoma cells transduced with the T cell costimulatory molecule OX40 ligand (OX40L) either alone (C26/OX4...

Giorgia Gri, Elena Gallo, Emma Di Carlo, Piero Musiani, Mario P Colombo (2003) J Immunol 170: 1 99-106

Antitumor effect of interleukin (IL)-12 in the absence of endogenous IFN-gamma: a role for intrinsic tumor immunogenicity and IL-15.

2011-06-13T12:48:00Z

IFN-gamma knockout mice (GKO) rejected C26 colon carcinoma cells transduced to secrete interleukin(IL)-12 but do not reject similarly transduced TSA mammary adenocarcinoma (C26/12 and TSA/12 cells, respectively). To determine whether such difference could be because of a different tumor response to IFN-gamma, we injected BALB/c mice with TSA, C26, and their IL-12-transduced counterparts rendered u...

Giorgia Gri, Claudia Chiodoni, Elena Gallo, Antonella Stoppacciaro, Foo Y Liew, Mario P Colombo (2002) Cancer Res 62: 15 4390-4397

Different requirements for alpha-galactosylceramide and recombinant IL-12 antitumor activity in the treatment of C-26 colon carcinoma hepatic metastases.

2011-06-13T12:48:00Z

The glycolipid alpha-galactosylceramide (alpha-GalCer), ligand of NKT cells, has been recently shown to induce antitumor immunity in mice through the induction of IL-12 production by dendritic cells. In the present study we compared alpha-GalCer and rIL-12 antitumor activities in the treatment of hepatic metastases of the C-26 murine colon carcinoma. We show that in immunocompetent mice the two mo...

C Chiodoni, A Stoppacciaro, S Sangaletti, G Gri, B Cappetti, Y Koezuka, M P Colombo (2001) Eur J Immunol 31: 10 3101-3110

Expression and function of IL-12 and IL-18 receptors on human tonsillar B cells.

2011-06-13T12:48:00Z

IL-12 activates murine and human B cells, but little information is available as to the expression and function of IL-12R on human B lymphocytes. Here we show that the latter cells, freshly isolated from human tonsils, expressed the transcripts of both beta1 and beta2 chains of IL-12R and that beta2 chain mRNA was selectively increased (4- to 5-fold) by incubation with Staphylococcus aureus Cowan ...

I Airoldi, G Gri, J D Marshall, A Corcione, P Facchetti, R Guglielmino, G Trinchieri, V Pistoia (2000) J Immunol 165: 12 6880-6888

Involvement of a p53-dependent pathway in rubella virus-induced apoptosis.

2011-06-13T12:48:00Z

In light of the important role of apoptotic cell death in the pathogenesis of several viral infections, we asked whether the cytopathogenicity evoked by rubella virus (RV) might also involve apoptotic mechanisms. The To-336 strain of RV induced apoptosis in Vero and RK-13 cells, but not in fibroblast cell lines. UV-inactivated RV virions did not elicit the apoptotic response, indicating that produ...

K Megyeri, K Berencsi, T D Halazonetis, G C Prendergast, G Gri, S A Plotkin, G Rovera, E Gönczöl (1999) Virology 259: 1 74-84

The interleukin-12-mediated pathway of immune events is dysfunctional in human immunodeficiency virus-infected individuals.

2011-06-13T12:48:00Z

Interleukin-12 (IL-12) is a potentially critical factor in the immune response against human immunodeficiency virus (HIV) because it is important for regulating proliferation and interferon-gamma (IFN-gamma) production by T cells and natural killer (NK) cells, antigen presentation and accessory cell function by macrophages and dendritic cells, and cytolytic activities of cytotoxic T-lymphocyte cel...

J D Marshall, J Chehimi, G Gri, J R Kostman, L J Montaner, G Trinchieri (1999) Blood 94: 3 1003-1011

Synergistic regulation of the human interleukin-12 p40 promoter by NFkappaB and Ets transcription factors in Epstein-Barr virus-transformed B cells and macrophages.

2011-06-13T12:48:20Z

Monocytes/macrophages produce interleukin-12 (IL-12) in response to pathogenic stimulation, whereas most Epstein-Barr virus-transformed (EBV+) B cells constitutively secrete IL-12. The molecular mechanism regulating the constitutive IL-12 gene expression in EBV+ B cells has not been addressed. In this study, using the EBV+ B cell line RPMI-8866, we localized to the human IL-12 p40 promoter two ess...

G Gri, D Savio, G Trinchieri, X Ma (1998) J Biol Chem 273: 11 6431-6438

Tumor cell responses to IFNgamma affect tumorigenicity and response to IL-12 therapy and antiangiogenesis.

2011-06-13T12:48:20Z

Expression of a dominant negative mutant IFNgammaR1 in murine SCK and K1735 tumor cells rendered them relatively unresponsive to IFNgamma in vitro and more tumorigenic and less responsive to IL-12 therapy in vivo. IL-12 induced histologic evidence of ischemic damage only in IFNgamma-responsive tumors, and in vivo Matrigel vascularization assays revealed that while IFNgamma-responsive and -unrespon...

C M Coughlin, K E Salhany, M S Gee, D C LaTemple, S Kotenko, X Ma, G Gri, M Wysocka, J E Kim, L Liu, F Liao, J M Farber, S Pestka, G Trinchieri, W M Lee (1998) Immunity 9: 1 25-34

Positive and negative regulation of interleukin-12 gene expression.

2011-06-13T12:48:20Z

Interleukin-12 (IL-12) is a pivotal cytokine representing the link between the cellular and humoral branches of an effective host immune defense apparatus. IL-12 is a heterodimer produced by phagocytic, B, dendritic, and possibly other accessory cells in both innate and adaptive immune responses. It is a key factor in the induction of T cell-dependent and independent activation of macrophages, gen...

X Ma, H Riemann, G Gri, G Trinchieri (1998) Eur Cytokine Netw 9: 3 Suppl 54-64

Differentiation of human NK cells into NK1 and NK2 subsets.

2011-06-13T12:48:20Z

Human NK cells cultured in the presence of IL-12 or IL-4 differentiate into cell populations with distinct patterns of cytokine secretion similar to Th1 and Th2 cells. NK cells grown in IL-12 (NK1) produce IL-10 and IFN-gamma, whereas NK cells grown in IL-4 (NK2) produce IL-5 and IL-13. Although these NK cell subsets do not differ in cytotoxic activity, NK1 cells express higher levels of cell surf...

D Peritt, S Robertson, G Gri, L Showe, M Aste-Amezaga, G Trinchieri (1998) J Immunol 161: 11 5821-5824

Interleukin-12: an immunoregulatory cytokine produced by B cells and antigen-presenting cells.

2011-06-13T12:48:20Z

Interleukin 12 (IL-12) is a heterodimeric protein produced by B cells, phagocytic cells, and other antigen-presenting cells. IL-12 was originally purified from the supernatant fluids of human EBV-transformed cell lines and later observed to be produced by the large majority of such cell lines, especially and at high levels from those derived from AIDS-associated lymphomas. However, phagocytic cell...

A Sartori, X Ma, G Gri, L Showe, D Benjamin, G Trinchieri (1997) Methods 11: 1 116-127

Immunomodulatory functions and molecular regulation of IL-12.

2011-06-13T12:48:20Z

X Ma, M Aste-Amezaga, G Gri, F Gerosa, G Trinchieri (1997) Chem Immunol 68: 1-22

Identification and characterization of a novel Ets-2-related nuclear complex implicated in the activation of the human interleukin-12 p40 gene promoter.

2011-06-13T12:48:20Z

Interleukin-12 (IL-12) is a proinflammatory cytokine produced by antigen-presenting cells in response to many microbial infections. IL-12 plays an important role in the generation of T helper type-1 cells, which favor cell-mediated immune response. IL-12 is composed of two different subunits, p40 and p35, whose expression can be regulated concomitantly or differentially. Monocytic cells, the major...

X Ma, M Neurath, G Gri, G Trinchieri (1997) J Biol Chem 272: 16 10389-10395

Earthworm leukocytes that are not phagocytic and cross-react with several human epitopes can kill human tumor cell lines.

2011-06-13T12:48:20Z

Earthworm coelomocytes (leukocytes) effect cytotoxicity at significantly high levels against the NK-sensitive, human tumor cell line, K562, and the NK-resistant targets (U937, BSM, CEM). By cytofluorimetric analyses using mouse anti-human monoclonal antibodies and by morphological evaluations, two types of coelomocytes were identified: (1) small (8-11 micron) electron-dense cells (SC): CD11a+, CD4...

A Cossarizza, E L Cooper, M M Suzuki, S Salvioli, M Capri, G Gri, D Quaglino, C Franceschi (1996) Exp Cell Res 224: 1 174-182

A novel ets-2-related nuclear factor is involved in transcriptional activation of the human interleukin-12 p40 gene promoter in response to interferon-gamma and LPS stimulation of monocytic cells.

2011-06-13T12:48:20Z

X Ma, G Gri, G Trinchieri (1996) Ann N Y Acad Sci 795: 357-360

The interleukin 12 p40 gene promoter is primed by interferon gamma in monocytic cells.

2011-06-13T12:48:20Z

Interleukin (IL) 12 is a proinflammatory cytokine produced by phagocytic cells, B cells, and other antigen-presenting cells that modulates adaptive immune responses by favoring the generation of T helper type 1 cells. IL-12 mediates some of its physiological activities by acting as a potent inducer of interferon (IFN) gamma production by T and natural killer cells. IFN-gamma enhances the ability o...

X Ma, J M Chow, G Gri, G Carra, F Gerosa, S F Wolf, R Dzialo, G Trinchieri (1996) J Exp Med 183: 1 147-157