Selective killing of hepatitis B envelope antigen-specific B cells by class I-restricted, exogenous antigen-specific T lymphocytes

Barnaba, Vincenzo; Franco, Alessandra; Alberti, Alfredo; Benvenuto, Roberta; Balsano, F

doi:10.1038/345258a0

Cited by 191 publications

(118 citation statements)

References 24 publications

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“…The capacity of in vivo activated HCV-specific CD8 + T cells to perform rapid effector function in vitro was also detected by ELISPOT assay, as described [23,31], through the stimulation of PBMC (2×10 5 /well) with a panel of well-defined HCV peptides for 4-6 h [23,31]. Autologous 51 Cr-labeled EBV-B cells were used as target cells, pulsed with the relevant peptides, in standard antigen-specific 6-h 51 Cr-release CTL assay with either fresh PBMC or HCV-specific CD8 + T cell lines, as previously described [54,55].…”

Section: Functional Assaysmentioning

confidence: 99%

Subversion of effector CD8⁺ T cell differentiation in acute hepatitis C virus infection: exploring the immunological mechanisms

et al. 2004

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Hallmark of acute hepatitis C virus (HCV) infection is a severe virus-specific effector CD8 + T cell dysfunction that seems to be a critical factor in preventing the resolution of infection and in favoring the onset of chronic liver immunopathology. We suggest that this dysfunction is critical in the establishment of HCV persistence, unless it is compensated by multispecific responses, as found in individuals resolving infection. Analyses on purified populations indicate that central memory HCV-specific CCR7 + /CD8 + T cells efficiently proliferate and differentiate in vitro, although the large population of memory effector CCR7 -cells found in the peripheral blood of acutely infected patients display poor effector functions ex vivo (semieffectors). However, we report strong evidence in support of IL-2 being capable of pushing semi-effector CTL to complete their effector cell program. Therefore, IL-2 deficiency during T cell activation may be responsible for the dichotomy between memory CTL expansion and incomplete effector differentiation shown in patients with acute HCV infection. These data are consistent with the possible therapeutic treatment with IL-2 to rebuild the effector T cell pool in these patients.

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Section: Functional Assaysmentioning

confidence: 99%

Subversion of effector CD8⁺ T cell differentiation in acute hepatitis C virus infection: exploring the immunological mechanisms

et al. 2004

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“…Peptides and tetramer were in part produced in our laboratory, as previously described [24,32], in part purchased from Proimmune Limited, Oxford, GB. Selected HCV-specific short-term lines were cloned by limiting dilution, as previously described [51].…”

Section: Cell Preparation and Stimulationmentioning

confidence: 99%

Subversion of effector CD8⁺ T cell differentiation in acute hepatitis C virus infection: the role of the virus

Accapezzato¹,

Francavilla²,

Rawson³

et al. 2004

Eur J Immunol

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In a companion study, we showed a dichotomy between the expansion of central memory (CCR7 + ) hepatitis C virus (HCV)-specific CTL and the incomplete memory effector differentiation in patients with acute HCV infection. Indeed, effector cells were unable to perform immediate functions, despite expressing the tissue-homing phenotype of effector memory cells (CCR7 -; semi-effectors). However, since they promptly differentiated into full-effectors upon IL-2 contact, we suggested that the inhibitory effect by environmental (possibly viral) factors on IL-2 production may have a pivotal role in generating the large population of semieffector CCR7 -/IFN-+ -CTL. In accord with this view, we report here strong evidence in support of circulating HCV core protein (HCVcore) playing a central role in inhibiting effector CTL differentiation, but not memory CTL expansion. The regulatory HCVcore effect is related to inhibition of the signal transduction pathway instrumental for IL-2 production, supporting the evidence that IL-2 was capable both of pushing semi-effector CTL to complete their effector cell program and of restoring the HCVcore-dependent inhibitory effect. Therefore, the strength of CTL activation is dependent on the balance between the threshold of stimulatory signals and the viral interference capacities provided during priming.

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“…In vitro studies showed that murine B lymphoblasts [13] or activated human B lymphocytes [14] efficiently process and present internalized viral antigens along the MHC class I pathway to virus specific CTL. Using a similar rationale, we showed that murine B lymphoma cells stably transfected with an immunoglobulin (Ig) gene coding for a CTL viral peptide process and present the peptide to cloned CD8 T cells [15].…”

Section: Introductionmentioning

confidence: 99%

CD8 T cell priming by B lymphocytes is CD4 help dependent

Castiglioni¹,

Gerloni²,

Cortez-Gonzalez³

et al. 2005

Eur J Immunol

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While it is generally accepted that B lymphocytes can present antigen and activate CD4 T cells, priming of CD8 T cells by B lymphocytes remains controversial. Recently, we showed that mice injected with genetically programmed B lymphocytes generate antigen specific CD4 and CD8 T cell responses in vivo that could also be induced in mice lacking functional dendritic cells. To gain further insights into the requirements for T cell priming by antigen-presenting B lymphocytes, in vitro experiments were performed using ovalbumin (OVA) and OVA-specific TCR-transgenic CD4 and CD8 T cells. We found that while B lymphocytes can directly prime CD4 T cells, the activation of CD8 T cells requires T cell help. Transfer experiments show that help can either be contact dependent or be mediated by soluble factors in the supernatants of activated OVAspecific CD4 T cells. Furthermore, the effect of activated CD4 T cells can be replaced by soluble recombinant IL-4. Collectively, the data show the existence of different requirements for priming of CD4 and CD8 T cells and point to the previously unappreciated fact that the induction of CD8 T cell responses by B lymphocytes requires T cell help.

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Selective killing of hepatitis B envelope antigen-specific B cells by class I-restricted, exogenous antigen-specific T lymphocytes

Cited by 191 publications

References 24 publications

Subversion of effector CD8⁺ T cell differentiation in acute hepatitis C virus infection: exploring the immunological mechanisms

Subversion of effector CD8⁺ T cell differentiation in acute hepatitis C virus infection: exploring the immunological mechanisms

Subversion of effector CD8⁺ T cell differentiation in acute hepatitis C virus infection: the role of the virus

CD8 T cell priming by B lymphocytes is CD4 help dependent

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Selective killing of hepatitis B envelope antigen-specific B cells by class I-restricted, exogenous antigen-specific T lymphocytes

Cited by 191 publications

References 24 publications

Subversion of effector CD8+ T cell differentiation in acute hepatitis C virus infection: exploring the immunological mechanisms

Subversion of effector CD8+ T cell differentiation in acute hepatitis C virus infection: exploring the immunological mechanisms

Subversion of effector CD8+ T cell differentiation in acute hepatitis C virus infection: the role of the virus

CD8 T cell priming by B lymphocytes is CD4 help dependent

Contact Info

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Subversion of effector CD8⁺ T cell differentiation in acute hepatitis C virus infection: exploring the immunological mechanisms

Subversion of effector CD8⁺ T cell differentiation in acute hepatitis C virus infection: exploring the immunological mechanisms

Subversion of effector CD8⁺ T cell differentiation in acute hepatitis C virus infection: the role of the virus