Immunoblot detection of viral protein Nef. Actin expression was used as protein loading control. ... more Immunoblot detection of viral protein Nef. Actin expression was used as protein loading control. This image is representative of experiments carried out in triplicate. (DOCX 1588Â kb)
Long-term immunological memory represents a unique performance of the adaptive immunity selected ... more Long-term immunological memory represents a unique performance of the adaptive immunity selected during evolution to support long-term survival of species in vertebrates, through protection against dangerous “invaders”, namely, infectious agents or unwanted (e.g., tumor) cells. The balance between the development of T cell memory and various mechanisms of immunoregulation (namely, T cell effector exhaustion and regulatory T cell suppression) dictates the fate in providing protection or not in different conditions, such as (acute or chronic) infection, vaccination, cancer, and autoimmunity. Here, these different environments are taken in consideration to outline the up-to-date cellular and molecular features regulating the development or damping of immunological memory and to delineate therapeutic strategies capable to improve or control it, in order to address pathological contexts, such as infection, tumor, and autoimmunity.
Advances in Experimental Medicine and Biology, 2020
In this chapter, we discuss the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) infec... more In this chapter, we discuss the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in the establishment of hepatocellular carcinoma (HCC), highlighting the key role of the multiple, non-mutually exclusive, pathways involved in the modulation of immune responses and in the orchestration of a chronic low-level inflammation state favouring HCC development. In particular, we discuss (i) HCC as a classical paradigm of inflammation-linked cancer; (ii) the role of the most relevant inflammatory cytokines involved (i.e. IL-6, TNF-α, IL-18, IL-1β, TGF-β IL-10); (iii) the role of T cell exhaustion by immune checkpoints; (iv) the role of the Wnt3a/β-catenin signalling pathway and (v) the role of different subsets of suppressor cells.
Anecdotal case reports, amplified by mass media and internet-based opinion groups, have recently ... more Anecdotal case reports, amplified by mass media and internet-based opinion groups, have recently indicated vaccinations as possibly responsible for autoimmunity/lymphoproliferation development. Multiply vaccinated Italian military personnel (group 1, operating in Italy, group 2, operating in Lebanon) were followed-up for nine months to monitor possible post-vaccine autoimmunity/lymphoproliferation onset. No serious adverse event was noticed in both groups. Multivariate analysis of intergroup differences only showed a significant association between lymphocyte increase and tetanus/diphtheria vaccine administration. A significant post-vaccine decrease in autoantibody positivity was observed. Autoantibodies were also studied by microarray analysis of self-proteins in subjects exposed to ≥4 concurrent vaccinations, without observing significant difference among baseline and one and nine months post-vaccine. Moreover, HLA-A2 subjects have been analyzed for the possible CD8T-cell response...
Summary T cells are made tolerant only to those self-peptides that are presented in sufficient am... more Summary T cells are made tolerant only to those self-peptides that are presented in sufficient amounts by antigen-presenting cells. They ignore cryptic self-determinants, such as either those not generated by processing machinery or generated in insufficient amounts. It is anticipated that mechanisms that either change antigen processing or increase the yield of previously "invisible" peptides may be capable of inducing
Here we show that apoptotic cells overexpress vinculin and are ingested by dendritic cells, which... more Here we show that apoptotic cells overexpress vinculin and are ingested by dendritic cells, which subsequently cross-prime vinculin-specific cytotoxic T lymphocytes (CTLs). Successful cross-priming requires that the apoptotic cells provide maturation signals to dendritic cells through CD40-CD40 ligand (CD40L) interactions. If apoptotic cells are CD40L-, the help of a third T cell is needed for priming, indicating a regulatory role for apoptotic cells in determining priming or tolerance. Vinculin-specific CTL priming is also related to apoptosis in vivo, given that in HIV-seropositive individuals, the frequency of specific CTLs depends on the proportion of peripheral CD40L+ apoptotic cells.
International Archives of Allergy and Immunology, 2014
A variety of physiological and pathological conditions may induce cell death. Therefore, it is re... more A variety of physiological and pathological conditions may induce cell death. Therefore, it is reasonable that apoptotic cells send different signals promoting either tolerance or immune responses. Many factors influence the type of response, such as the quality (e.g. bearing or released factors, activation state), the timing and the site of cell death. In particular, the activation state of apoptotic lymphocytes (CD40L expression) may be crucial in determining the fate of their cross-presentation, i.e. cross-tolerance versus cross-priming. The cross-presentation of apoptotic activated CD40L+ T cells determines the cross-priming of apoptotic epitope-specific CD8+ T cells. These autoreactive CD8+ T cells are observed in diseases with a sustained component of chronic inflammation such as chronic viral infections and systemic autoimmune diseases. We have explored this phenomenon in HIV and chronic hepatitis C virus infections as well as in multiple sclerosis and rheumatoid arthritis, a...
Advances in Experimental Medicine and Biology, 2013
Cross-presentation of several long-lived antigens associated with apoptotic T cells requires casp... more Cross-presentation of several long-lived antigens associated with apoptotic T cells requires caspase-dependent cleavage to efficiently deliver antigenic fragments to the processing machinery of antigen-presenting cells. The resulting emergence of a large population of autoreactive CD8(+) T effector cells specific for apoptotic T cell-associated self-epitopes plays a key role in improving immunopathology in several infections and autoimmune diseases. Importantly, they endow mixed polyfunctional type-1, type-2, and type-17 responses and correlate with the chronic progression of various pathological conditions. This evolution is related to the selection of autoreactive CD8(+) T cells with higher T cell receptor avidity, whereas those with lower avidity undergo prompt contraction in patients undergoing disease resolution. The development of mixed responses with divergent differentiation requirements is consistent with distinct sites or kinetics of CD8(+) T cell priming in vivo. Therefore, we propose a strict link among cross-presentation of apoptotic T cells, the generation of high frequencies of mixed autoreactive CD8(+) T cells producing a broad array of cytokines (IFN-γ, IL-17, IL-4, IL-2, etc.), and the progression towards chronic inflammatory diseases.
Immunoblot detection of viral protein Nef. Actin expression was used as protein loading control. ... more Immunoblot detection of viral protein Nef. Actin expression was used as protein loading control. This image is representative of experiments carried out in triplicate. (DOCX 1588Â kb)
Long-term immunological memory represents a unique performance of the adaptive immunity selected ... more Long-term immunological memory represents a unique performance of the adaptive immunity selected during evolution to support long-term survival of species in vertebrates, through protection against dangerous “invaders”, namely, infectious agents or unwanted (e.g., tumor) cells. The balance between the development of T cell memory and various mechanisms of immunoregulation (namely, T cell effector exhaustion and regulatory T cell suppression) dictates the fate in providing protection or not in different conditions, such as (acute or chronic) infection, vaccination, cancer, and autoimmunity. Here, these different environments are taken in consideration to outline the up-to-date cellular and molecular features regulating the development or damping of immunological memory and to delineate therapeutic strategies capable to improve or control it, in order to address pathological contexts, such as infection, tumor, and autoimmunity.
Advances in Experimental Medicine and Biology, 2020
In this chapter, we discuss the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) infec... more In this chapter, we discuss the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in the establishment of hepatocellular carcinoma (HCC), highlighting the key role of the multiple, non-mutually exclusive, pathways involved in the modulation of immune responses and in the orchestration of a chronic low-level inflammation state favouring HCC development. In particular, we discuss (i) HCC as a classical paradigm of inflammation-linked cancer; (ii) the role of the most relevant inflammatory cytokines involved (i.e. IL-6, TNF-α, IL-18, IL-1β, TGF-β IL-10); (iii) the role of T cell exhaustion by immune checkpoints; (iv) the role of the Wnt3a/β-catenin signalling pathway and (v) the role of different subsets of suppressor cells.
Anecdotal case reports, amplified by mass media and internet-based opinion groups, have recently ... more Anecdotal case reports, amplified by mass media and internet-based opinion groups, have recently indicated vaccinations as possibly responsible for autoimmunity/lymphoproliferation development. Multiply vaccinated Italian military personnel (group 1, operating in Italy, group 2, operating in Lebanon) were followed-up for nine months to monitor possible post-vaccine autoimmunity/lymphoproliferation onset. No serious adverse event was noticed in both groups. Multivariate analysis of intergroup differences only showed a significant association between lymphocyte increase and tetanus/diphtheria vaccine administration. A significant post-vaccine decrease in autoantibody positivity was observed. Autoantibodies were also studied by microarray analysis of self-proteins in subjects exposed to ≥4 concurrent vaccinations, without observing significant difference among baseline and one and nine months post-vaccine. Moreover, HLA-A2 subjects have been analyzed for the possible CD8T-cell response...
Summary T cells are made tolerant only to those self-peptides that are presented in sufficient am... more Summary T cells are made tolerant only to those self-peptides that are presented in sufficient amounts by antigen-presenting cells. They ignore cryptic self-determinants, such as either those not generated by processing machinery or generated in insufficient amounts. It is anticipated that mechanisms that either change antigen processing or increase the yield of previously "invisible" peptides may be capable of inducing
Here we show that apoptotic cells overexpress vinculin and are ingested by dendritic cells, which... more Here we show that apoptotic cells overexpress vinculin and are ingested by dendritic cells, which subsequently cross-prime vinculin-specific cytotoxic T lymphocytes (CTLs). Successful cross-priming requires that the apoptotic cells provide maturation signals to dendritic cells through CD40-CD40 ligand (CD40L) interactions. If apoptotic cells are CD40L-, the help of a third T cell is needed for priming, indicating a regulatory role for apoptotic cells in determining priming or tolerance. Vinculin-specific CTL priming is also related to apoptosis in vivo, given that in HIV-seropositive individuals, the frequency of specific CTLs depends on the proportion of peripheral CD40L+ apoptotic cells.
International Archives of Allergy and Immunology, 2014
A variety of physiological and pathological conditions may induce cell death. Therefore, it is re... more A variety of physiological and pathological conditions may induce cell death. Therefore, it is reasonable that apoptotic cells send different signals promoting either tolerance or immune responses. Many factors influence the type of response, such as the quality (e.g. bearing or released factors, activation state), the timing and the site of cell death. In particular, the activation state of apoptotic lymphocytes (CD40L expression) may be crucial in determining the fate of their cross-presentation, i.e. cross-tolerance versus cross-priming. The cross-presentation of apoptotic activated CD40L+ T cells determines the cross-priming of apoptotic epitope-specific CD8+ T cells. These autoreactive CD8+ T cells are observed in diseases with a sustained component of chronic inflammation such as chronic viral infections and systemic autoimmune diseases. We have explored this phenomenon in HIV and chronic hepatitis C virus infections as well as in multiple sclerosis and rheumatoid arthritis, a...
Advances in Experimental Medicine and Biology, 2013
Cross-presentation of several long-lived antigens associated with apoptotic T cells requires casp... more Cross-presentation of several long-lived antigens associated with apoptotic T cells requires caspase-dependent cleavage to efficiently deliver antigenic fragments to the processing machinery of antigen-presenting cells. The resulting emergence of a large population of autoreactive CD8(+) T effector cells specific for apoptotic T cell-associated self-epitopes plays a key role in improving immunopathology in several infections and autoimmune diseases. Importantly, they endow mixed polyfunctional type-1, type-2, and type-17 responses and correlate with the chronic progression of various pathological conditions. This evolution is related to the selection of autoreactive CD8(+) T cells with higher T cell receptor avidity, whereas those with lower avidity undergo prompt contraction in patients undergoing disease resolution. The development of mixed responses with divergent differentiation requirements is consistent with distinct sites or kinetics of CD8(+) T cell priming in vivo. Therefore, we propose a strict link among cross-presentation of apoptotic T cells, the generation of high frequencies of mixed autoreactive CD8(+) T cells producing a broad array of cytokines (IFN-γ, IL-17, IL-4, IL-2, etc.), and the progression towards chronic inflammatory diseases.
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Papers by Vincenzo Barnaba