Fabrizio Poccia

Istituto Sperimentale Italiano Lazzaro Spallanzani, Rivolta, Lombardy, Italy

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Publications (115)479.25 Total impact

  • Marie-Lise Gougeon · Fabrizio Poccia · Séverine Boullier ·

    Springer Seminars in Immunopathology 04/2012; 22(3):251-263. DOI:10.1007/s002810000046 · 4.55 Impact Factor
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    ABSTRACT: The CD94/NKG2 complex is expressed on T and NK lymphocytes. CD94 molecules covalently associate to activating or inhibitory NKG2 molecules, and their expression finely tunes cell responses. Human γδ T cells express several NKRs. Expression of these receptors is confined to the cytolytic Vδ2 subset, which coexpresses the FcγRIII CD16 and CD45RA and has been defined as Vγ9Vδ2 T(EMRA) cells. We show that the CD94/NKG2C complex, associated with KARAP/DAP12, is fully functional in γδ T cells, as determined by measuring IFN-γ production, T cell proliferation, and cytolytic activity by γδ lymphocytes. In contrast, NKG2A expression was found on all γδ T cell memory subsets, suggesting a crucial role of the inhibitory signal provided by this receptor on γδ T cell responses. Moreover, we found Vγ9Vδ2 T(EMRA), NK, and CD8+ αβ T cells coexpressing NKG2A and NKG2C receptors. Functional experiments showed that the inhibitory signal mediated by the NKG2A receptor prevails when double-positive cells are activated. Finally, NKG2A expression on γδ LDGL correlates with asymptomatic pathology, even in the presence of NKG2C coexpression, whereas in symptomatic patients affected by severe disease, the inhibitory NKG2A receptor is absent, and a variety of activatory NKRs was found. We propose that the silent behavior of γδ cells in LDGL patients is a result of effective inhibitory HLA class I receptors.
    Journal of leukocyte biology 10/2010; 89(1):75-84. DOI:10.1189/jlb.0710413 · 4.29 Impact Factor
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    Nephrology Reviews 06/2009; 2(3). DOI:10.4081/hmr.v2i3.367
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    A Martino · F Poccia ·

    Nephrology Reviews 06/2009; 2(3). DOI:10.4081/hmr.v2i3.363
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    ABSTRACT: The Vgamma9 Vdelta2 T cells mediate rapid, innate-like immune responses to pathogens and are important in several key immunoregulatory pathways, including those involved in infections and tumor development. Vgamma9 Vdelta2 T cells respond to low molecular weight isoprenoid phosphoantigens; the prototypic stimulatory compound is isopentenylpyrophosphate (IPP), an alkylphosphate intermediate of mevalonate metabolism that elicits proliferative, cytotoxic, and cytokine secretion responses. We studied the replacement of the pyrophosphate moiety with the thiopyrophosphate bioisostere, synthesizing thioanalogues of IPP and 4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP, the most potent natural antigen known to date). Once their in vitro efficacy and stability had been demonstrated, we synthesized a small library of compounds through the development of an innovative solid-phase strategy. Biological results confirmed thioHMBPP to be the best compound of this first series. Future aims are (i) the exploitation of the parallel solid-phase strategy to further explore structure-activity relationships of this new class of synthetic antigens and (ii) the determination of the PK/PD profile of thioHMBPP.
    Journal of Medicinal Chemistry 06/2009; 52(12):3716-22. DOI:10.1021/jm900054u · 5.45 Impact Factor
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    ABSTRACT: Objective: γδ T cells bearing the Vγ9Vδ2 T-cell receptor exert many antiviral effector functions in humans, including release of anti-HIV factors and direct cytotoxicity against virus-infected cells. Moreover, they are known to activate dendritic cells, improving antigen presentation function. After HIV infection, Vγ9Vδ2 T-cell number and reactivity are rapidly affected and they decrease upon disease progression. Bisphosphonate drugs such as zoledronic acid (Zol), used to treat bone diseases, have been shown to induce in vivo, in combination with interleukin-2, Vγ9Vδ2 T-cells' activation. The aim of this work was to verify whether the administration of Zol in combination with interleukin-2 in HIV-infected patients might improve Vγ9Vδ2 T-cell function, including immune adjuvancy mediated by γδ-dendritic cell cross-talk. Design and methods: In HIV patients naive to antiretroviral therapy, we analyzed the effect of combined Zol and interleukin-2 treatment, in comparison to Zol alone, on Vγ9Vδ2 T-cell number, maturation and function, on dendritic cell activation and on HIV-specific CD8 T-cell response. Results: Zol and interleukin-2-combined treatment induced in-vivo Vγ9Vδ2 T-cell expansion and maturation. Paralleling Vγ9Vδ2 T-cell activation, increased dendritic cell maturation and HIV-specific CD8 T-cell responses were found. Conclusion: The specific modulation of Vγ9Vδ2 T-cell number and responsiveness after HIV infection may be at least transiently restored in vivo by Zol and interleukin-2 treatment. In this way, the immune effector mechanisms, secondary to Vγ9Vδ2 T-cell activation, were improved, suggesting a possible adjuvancy role of Zol and interleukin-2 treatment in restoring innate and specific competence in HIV-infected persons.
    AIDS 03/2009; 23(5):555-565. DOI:10.1097/QAD.0b013e3283244619 · 5.55 Impact Factor
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    ABSTRACT: IntroductionAmino-bisphosphonates are potent activators of human γδ T cells. The aim of our study was to evaluate the immunomodulating properties of a single-dose of zoledronic acid (ZA) on γδ T cells in a select group of disease-free breast cancer patients with osteopenia. Materials and methods Blood samples were obtained, from 23 patients, before and 7, 28, 56, 90 and 180days after a single-dose (4mg) of ZA and analyzed by flow cyometry. ResultsA significant decrease of the different γδ T cell subsets was observed: Naïve (CD3+/Vdelta2+/CD45RA+/CD27+) after 180days (P<0.01); Central Memory (CD3+/Vdelta2+/CD45RA-CD27+) after 28 (P<0.05), 90 (P<0.01) and 180days (P<0.01); and Effector Memory (CD3+/Vdelta2+/CD45RA-/CD27-) after 56 (P<0.01) and 90 (P<0.05) days. Based on the observed γδ T cells kinetics patients could be divided in two groups: “responders” that showed a significant decrease in total numbers of γδ T cells and “non-responders” that showed no significant change. However, in vitro phosphoantigen stimulation of patients cells did not show significant differences in terms of IFN-γ response by Vδ2 T cells. ConclusionWe describe for the first time a long-lasting activation of effector subsets of γδ T cells in disease-free breast cancer patients after a single-dose of ZA. Our results highlight the need to further investigate the clinical significance of the immunomodulating properties of N-BPs.
    Cancer Immunology and Immunotherapy 01/2009; 58(1):31-38. DOI:10.1007/s00262-008-0521-6 · 3.94 Impact Factor

  • Bone 03/2008; 42. DOI:10.1016/j.bone.2007.12.206 · 3.97 Impact Factor
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    ABSTRACT: Avian influenza virus (H5N1) can be transmitted to humans, resulting in a severe or fatal disease. The aim of this study was to evaluate the immune cross-reactivity between human and avian influenza (H5N1) strains in healthy donors vaccinated for seasonal influenza A (H1N1)/(H3N2). A small frequency of CD4 T cells specific for subtype H5N1 was detected in several persons at baseline, and seasonal vaccine administration enhanced the frequency of such reactive CD4 T cells. We also observed that seasonal vaccination is able to raise neutralizing immunity against influenza (H5N1) in a large number of donors. No correlation between influenza-specific CD4 T cells and humoral responses was observed. N1 may possibly be a target for both cellular and humoral cross-type immunity, but additional experiments are needed to clarify this point. These findings highlight the possibility of boosting cross-type cellular and humoral immunity against highly pathogenic avian influenza A virus subtype H5N1 by seasonal influenza vaccination.
    Emerging infectious diseases 02/2008; 14(1):121-8. DOI:10.3201/eid1401.061283 · 6.75 Impact Factor
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    ABSTRACT: GB virus C (GBV-C) coinfection has a protective role in Human Immunodeficiency Virus (HIV) infection, and increases the duration of suppression of HIV-1 viremia in patients under Highly Active Anti-Retroviral Therapy (HAART). Since innate antiviral response may be involved in the protection, we analyzed the possible role of GBV-C as activator of innate immunity. To this aim, we measured the extent of activation of the interferon (IFN) system and of circulating Dendritic Cells (DC) in vivo, and the ability of GBV-C to activate these functions in vitro. Activation of IFN system and of circulating DC was compared in GBV-positive and -negative HIV-1 co-infected patients with HAART-driven suppression of HIV-1 viremia. Endogenous levels of IFN-gamma and RNA-dependent protein kinase (PKR) mRNA were significantly higher in peripheral blood mononuclear cells (PBMC) from GBV-C-positive when compared to GBV-C-negative patients. IFN-gamma expression was correlated with all the Interferon response genes (IRGs) and with GBV-C viremia. The frequency of circulating plasmacytoid DC (pDC) expressing the CD80 activation marker was increased in GBV-C-positive patients, and was correlated with GBV-C viral load. In vitro experiments indicated that GBV-C is able to induce IFN-gamma expression in PBMC. In addition, in PBMC cultures GBV-C induced an increase of CD80 expression by pDC, that was reduced by antibody to IFN-gamma. Our data indicate that in HIV-positive patients GBV-C coinfection promotes the activation of IFN-gamma and downstream IRG expression, as well as with the activation/maturation of circulating pDC. GBV-C-driven IFN-gamma activation is, at least in part, responsible for the increased maturation of pDC. This crosstalk may suggest a role for GBV-C coinfection in boosting the innate antiviral response to HIV infection.
    International journal of immunopathology and pharmacology 01/2008; 21(1):161-71. · 1.62 Impact Factor
  • Angelo Martino · Fabrizio Poccia ·
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    ABSTRACT: The knowledge of several signals influencing Dendritic Cell (DC) functions is crucial to manipulate the immune system for new vaccination therapies. Our recent findings provide a new model of intervention on DC system suggesting novel therapeutic implications. T, NK, and gammadelta T cell stimuli may enhance DC maturation, Th polarization and trigger the adaptive immune response. Regulatory effects of gammadelta T cells on inflammation and immune responses may be mediated by their interaction with DCs and they are analyzed in the last years in humans and mice. In humans, Vgamma9Vdelta2 T cells represent the most part of circulating gammadelta T cells and are activated by non-peptidic molecules derived from different microorganisms or abnormal metabolic routes. They share both NK-like and effector/memory T cell features, and among these the possibility to interact with DCs. Co-culture of immature DCs with activated Vgamma9Vdelta2 T cells allows DCs to acquire features of mature DCs complementing the migratory activity, up-regulating the chemokine receptors, and antigen presentation. Similarly to the NK-derived signals, DC activation is mostly mediated by soluble factors secreted by gammadelta T cells. Many non-peptidic molecules including nitrogen-containing bisphosphonates and pyrophosphomonoester drugs stimulate the activity of Vgamma9Vdelta2 T cells in vitro and in vivo. The relatively low in vivo toxicity of many of these drugs makes possible novel vaccine and immune-based strategies, through DCs, for infectious and neoplastic diseases.
    Current Molecular Medicine 12/2007; 7(7):658-73. · 3.62 Impact Factor
  • Angelo Martino · Fabrizio Poccia ·
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    ABSTRACT: The knowledge of several signals influencing Dendritic Cell (DC) functions is crucial to manipulate the immune system for new vaccination therapies. Our recent findings provide a new model of intervention on DC system suggesting novel therapeutic implications. T, NK, and gamma delta T cell stimuli may enhance DC maturation, Th polarization and trigger the adaptive immune response. Regulatory effects of gamma delta T cells on inflammation and immune responses may be mediated by their interaction with DCs and they are analyzed in the last years in humans and mice. In humans, V gamma 9V delta 2 T cells represent the most part of circulating gamma delta T cells and are activated by non-peptidic molecules derived from different microorganisms or abnormal metabolic routes. They share both NK-like and effector/memory T cell features, and among these the possibility to interact with DCs. Coculture of immature DCs with activated V gamma 9V delta 2T cells allows DCs to acquire features of mature DCs complementing the migratory activity, up-regulating the chemokine receptors, and antigen presentation. Similarly to the NK-derived signals, DC activation is mostly mediated by soluble factors secreted by gamma delta T cells.
    Current Molecular Medicine 11/2007; 7(7):658-673. DOI:10.2174/156652407782564345 · 3.62 Impact Factor
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    Angelo Martino · Rita Casetti · Alessandra Sacchi · Fabrizio Poccia ·
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    ABSTRACT: In humans, innate immune recognition of mycobacteria, including Mycobacterium tuberculosis and bacillus Calmette-Guérin (BCG), is a feature of cells as dendritic cells (DC) and gammadelta T cells. In this study, we show that BCG infection of human monocyte-derived DC induces a rapid activation of Vgamma9Vdelta2 T cells (the major subset of gammadelta T cell pool in human peripheral blood). Indeed, in the presence of BCG-infected DC, Vgamma9Vdelta2 T cells increase both their expression of CD69 and CD25 and the production of TNF-alpha and IFN-gamma, in contrast to DC treated with Vgamma9Vdelta2 T cell-specific Ags. Without further exogenous stimuli, BCG-infected DC expand a functionally cytotoxic central memory Vgamma9Vdelta2 T cell population. This subset does not display lymph node homing receptors, but express a high amount of perforin. They are highly efficient in the killing of mycobacterial-infected primary monocytes or human monocytic THP-1 cells preserving the viability of cocultured, infected DC. This study provides further evidences about the complex relationship between important players of innate immunity and suggests an immunoregulatory role of Vgamma9Vdelta2 T cells in the control of mycobacterial infection.
    The Journal of Immunology 10/2007; 179(5):3057-64. DOI:10.4049/jimmunol.179.5.3057 · 4.92 Impact Factor
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    ABSTRACT: In some early-treated HIV-positive patients, Structured Treatment Interruption (STI) is associated to spontaneous control of viral rebound. Thus, in this clinical setting, we analyzed the immunological parameters associated to viral control. Two groups of early treated patients who underwent STI were retrospectively defined, according to the ability to spontaneously control HIV replication (Controller and Non-controller). Plasma cytokine levels were analyzed by multiplex analysis. CD8 T cell differentiation was determined by polychromatic flow cytometry. Antigen-specific IFN-gamma production was analyzed by ELISpot and intracellular staining after stimulation with HIV-peptides. Long-term Elispot assays were performed in the presence or absence of IL-15. Plasma IL-15 was found decreased over a period of time in Non-Controller patients, whereas a restricted response to Gag (aa.167-202 and 265-279) and Nef (aa.86-100 and 111-138) immunodominant epitopes was more frequently observed in Controller patients. Interestingly, in two Non-Controller patients the CD8-mediated T cells response to immunodominant epitopes could be restored in vitro by IL-15, suggesting a major role of cytokine homeostasis on the generation of protective immunity. In early-treated HIV+ patients undergoing STI, HIV replication control was associated to CD8 T cell maturation and sustained IL-15 levels, leading to HIV-specific CD8 T cell responses against selected Gag and Nef epitopes.
    International journal of immunopathology and pharmacology 07/2007; 20(3):473-85. · 1.62 Impact Factor

  • International Journal of Antimicrobial Agents 03/2007; 29. DOI:10.1016/S0924-8579(07)70236-4 · 4.30 Impact Factor
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    ABSTRACT: Human immunodeficiency virus (HIV)-induced immunodeficiency and immune-system aging share some analogies. Since Werner (WRN) and Bloom (BLM) helicases are crucial in cell repair and aging, their peripheral blood mononuclear cells (PBMC) mRNA levels were compared in HIV-1 infected patients and in normal donors. The mean levels of WRN mRNA were 3.7-fold higher in PBMCs from HIV-1 infected individuals in comparison to healthy donors, whereas BLM mRNA mean levels were slightly higher, although not significantly. WRN increase was positively correlated to CD4 and CD8 T-cell numbers, and also the percentage of naive T lymphocytes, and was observed also in T-cell subsets. Interestingly, a general trend toward increased WRN mRNA levels in individuals with lower viral load was observed, without association with patient age, time of seroconversion, and on/off antiretroviral therapy regimen. On the whole, this study shows that WRN and BLM are differentially modulated in HIV infection, as WRN--but not BLM--is significantly increased, suggesting that mechanisms different from defect or loss of helicase function, observed in WRN and BLM syndromes, may be at the basis of T-cell aging in HIV infection.
    Human Immunology 03/2007; 68(2):91-9. DOI:10.1016/j.humimm.2006.11.004 · 2.14 Impact Factor
  • Angelo Martino · Rita Casetti · Fabrizio Poccia ·
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    ABSTRACT: Since drug-activated gammadelta T cells promote dendritic cell (DC) maturation, we analyzed the effect of combining gammadelta T cell specific drugs with BCG in vitro. BCG-induced DC maturation was increased by bromohydrin-pirophosphate (BrHPP) or zoledronate (Zol)-activated gammadelta T cells. Specifically, the co-culture with activated Vgamma9Vdelta2 T cells with BCG-infected DC resulted in a significant increase of the expression of CD80, CD86, CD40 and CD25 molecules on DC. Moreover, DC were able to produce increased levels of TNF-alpha and synthesize ex novo IL-15 without altering the IL-10/IL-12 immunoregulatory pathway. Finally, the Th1 immunity induced by BCG-infected DC on naïve CD4 T cells was increased by gammadelta T cell activation with BrHpp or Zol. These data indicate that gammadelta T cell triggering drugs could be used to enhance the BCG induced Th1 immunity.
    Vaccine 02/2007; 25(6):1023-9. DOI:10.1016/j.vaccine.2006.09.070 · 3.62 Impact Factor
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    ABSTRACT: Existing data on the effect of treatment of latent tuberculosis infection (LTBI) on T-cell responses to Mycobacterium tuberculosis (MTB)-specific antigens are contradictory. Differences in technical aspects of the assays used to detect this response and populations studied might explain some of these discrepancies. In an attempt to find surrogate markers of the effect of LTBI treatment, it would be important to determine whether, among contacts of patients with contagious tuberculosis, therapy for LTBI could cause changes in MTB-specific immune responses to a variety of RD1-antigens. In a longitudinal study, 44 tuberculin skin test+ recent contacts were followed over a 6-month period and divided according to previous exposure to MTB and LTBI treatment. The following tests which evaluate IFN-gamma responses to RD1 antigens were performed: QuantiFERON TB Gold, RD1 intact protein- and selected peptide-based assays. Among the 24 contacts without previous exposure that completed therapy, we showed a significant decrease of IFN-gamma response in all tests employed. The response to RD1 selected peptides was found to be more markedly decreased compared to that to other RD1 antigens. Conversely, no significant changes in the response to RD1 reagents were found in 9 treated subjects with a known previous exposure to MTB and in 11 untreated controls. These data suggest that the effect of INH prophylaxis on RD1-specific T-cell responses may be different based on the population of subjects enrolled (recent infection versus re-infection) and, to a minor extent, on the reagents used.
    Respiratory research 02/2007; 8(1):5. DOI:10.1186/1465-9921-8-5 · 3.09 Impact Factor
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    ABSTRACT: Sphingosine 1-phosphate (S1P) is a lipidic messenger known to exert several physiological functions within the cell. We tested here whether the stimulation of human monocytes with different doses of S1P might interfere with their differentiation into competent dendritic cells (DC). Monocytes cultured with granulocyte macrophage colony stimulating factor, interleukin-4 (IL-4) and S1P differentiated into a DC population lacking CD1a molecules on the surface and acquired some aspects of mature DC (mDC), though in the absence of maturation stimuli. When stimulated with lipopolisaccharide (LPS), CD1a(-) DC produce high amounts of tumour necrosis factor-alpha and IL-10, but not IL-12. Accordingly, these CD1a(-) DC were not capable of stimulating allogenic T lymphocytes so well as CD1a(+) DC generated from untreated monocytes and maturated with LPS. S1P monocyte-derived DC lost their polarizing capacity abrogating the production of gamma-interferon/IL-4 by co-cultured naïve CD4(+)CD45RA(+) T cells. Our findings suggest a mechanism through which S1P can favour the development of immune-related pathological states.
    Scandinavian Journal of Immunology 02/2007; 65(1):84-91. DOI:10.1111/j.1365-3083.2006.01860.x · 1.74 Impact Factor
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    ABSTRACT: Phosphoantigens are mycobacterial non-peptide antigens that might enhance the immunogenicity of current subunit candidate vaccines for tuberculosis. However, their testing requires monkeys, the only animal models suitable for gammadelta T cell responses to mycobacteria. Thus here, the immunogenicity of 6-kDa early secretory antigenic target-mycolyl transferase complex antigen 85B (ESAT-6-Ag85B) (H-1 hybrid) fusion protein associated or not to a synthetic phosphoantigen was compared by a prime-boost regimen of two groups of eight cynomolgus. Although phosphoantigen activated immediately a strong release of systemic Th1 cytokines (IL-2, IL-6, IFN-gamma, TNF-alpha), it further anergized blood gammadelta T lymphocytes selectively. By contrast, the hybrid H-1 induced only memory alphabeta T cell responses, regardless of phosphoantigen. These latter essentially comprised cytotoxic T lymphocytes specific for Ag85B (on average + 430 cells/million PBMC) and few IFN-gamma-secreting cells (+ 40 cells/million PBMC, equally specific for ESAT-6 and for Ag85B). Hence, in macaques, a prime-boost with the H-1/phosphoantigen subunit combination induces two waves of immune responses, successively by gammadelta T and alphabeta T lymphocytes.
    European Journal of Immunology 02/2007; 37(2):549-65. DOI:10.1002/eji.200636343 · 4.03 Impact Factor

Publication Stats

3k Citations
479.25 Total Impact Points


  • 2008-2009
    • Istituto Sperimentale Italiano Lazzaro Spallanzani
      Rivolta, Lombardy, Italy
  • 2001-2008
    • National Institute of Allergy and Infectious Diseases
      베서스다, Maryland, United States
  • 2007
    • Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana
      Roma, Latium, Italy
  • 2003-2007
    • Istituto Nazionale per le Malattie Infettive "L.Spallanzani"
      Roma, Latium, Italy
  • 2006
    • Istituto Nazionale Tumori "Fondazione Pascale"
      Napoli, Campania, Italy
  • 2000
    • Sapienza University of Rome
      • Department of Clinical Medicine
      Roma, Latium, Italy
  • 1992-2000
    • University of Rome Tor Vergata
      • Dipartimento di Biologia
      Roma, Latium, Italy
  • 1998
    • University of Wisconsin, Madison
      • Department of Medical Microbiology and Immunology
      Madison, MS, United States
  • 1995-1996
    • Institut Pasteur
      Lutetia Parisorum, Île-de-France, France