Vgamma9Vdelta2 T cells represent a key subset in innate immunity. They represent 1-5% of the circulating T cells and can be massively activated by non peptidic compounds generated by metabolic pathways. The activation of Vgamma9Vdelta2 T cells results in killing of infected cells and in fast release of soluble factors with direct antimicrobial properties, as well as immunomodulatory activity. The main aim of this work was to define the antiviral mechanisms activity exploited by Vgamma9Vdelta2 T cells in order to evaluate their possible use as target for new immunotherapy. The antiviral activity of Vgamma9Vdelta2 T cells against SARS-CoV and HCV infections was evaluated. Health care workers who survived SARS-CoV infection showed a selective expansion of effector/memory Vgamma9Vdelta2 T cells which was associated with a higher anti SARS-CoV IgG titers, suggesting a possible involvement of Vgamma9Vdelta2 T cells in SARS immunosurveillance. In addition, in vitro experiments demonstrated that stimulated Vgamma9Vdelta2 T cells displays an IFN-gamma-dependent anti-SARS-CoV activity and are able to directly kill SARS-CoV infected cells. A similar analysis was performed using an in vitro model for HCV replication (HCV replicon system). The activation of Vγ9Vδ2 T cell was able to induce a strong inhibition of HCV replication, and this antiviral activity was mainly mediated by IFN-gamma production. Interestingly, drugs already in clinical use, such as Phosphostim and Zoledronate, known able to activate gammadelta T cells, were shown to induce the IFN-g-mediated inhibition of HCV replication, suggesting that the therapeutic activation of Vγ9Vδ2 T lymphocytes may represent an additional strategy to inhibit HCV replication and to restore a Th1 polarizes immune response in HCV-infected patients. Finally, we demonstrated that soluble factor released by Vgamma9Vdelta2 T cells are able to induce the activation of granulocytes with consequent release of alpha-defensins. Altogether, our results suggest that the activation of Vgamma9Vdelta2 T cells by using specific drugs may induce a direct antiviral activity and may result in granulocyte activation and alpha-defensins release. Thus, drugs targeting Vgamma9Vdelta2 T cells may be tested as new antiviral and immunomodulatory components in combined therapeutical strategies for infectious diseases.
Agrati, C. (2008). Antiviral activity of Vgamma9Vdelta2 T cells: a possible target for immunotherapy.
|Titolo:||Antiviral activity of Vgamma9Vdelta2 T cells: a possible target for immunotherapy|
|Data di pubblicazione:||14-lug-2008|
|Anno Accademico:||A.A. 2007/2008|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Tipologia:||Tesi di dottorato|
|Citazione:||Agrati, C. (2008). Antiviral activity of Vgamma9Vdelta2 T cells: a possible target for immunotherapy.|
|Appare nelle tipologie:||07 - Tesi di dottorato|
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