Claudia J Dembek

Publications (4)12.74 Total impact

• Article: OMIP-016: Characterization of antigen-responsive macaque and human T-cells.

  Sabrina Guenounou, Nathalie Bosquet, Claudia J Dembek, Roger Le Grand, Antonio Cosma
  Cytometry Part A 11/2012; · 3.73 Impact Factor
• Article: Longitudinal changes in HIV-1-specific T-cell quality associated with viral load dynamic.

  Claudia J Dembek, Sarah Kutscher, Simone Allgayer, Carolina Russo, Tanja Bauer, Dieter Hoffmann, Frank D Goebel, Johannes R Bogner, Volker Erfle, Ulrike Protzer, Antonio Cosma
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  ABSTRACT: Several correlates of HIV control have been described; however their predictive values remain unclear, since most studies have been performed in cross-sectional settings. We evaluated the cause and consequence relationship between quality of HIV-specific T-cell response and viral load dynamic in a temporal perspective. HIV-1-specific T-cell responses were monitored over 7 years in a patient that following treatment interruption maintained a stable/low viral set point for 3.1 years before control of viral replication was lost and antiretroviral therapy restarted. We observed that high frequencies of HIV-1-specific CD4 and CD8 T cells were unable to prevent loss of viral control. Gradual loss of functionality was observed in these responses, characterized by early loss of IL-2, viral load-dependent decrease of IFN-γ and CD154 expression as well as increase of MIP-1β production. Terminally differentiated HIV-1-specific CD8 T cells expressing CD45RA were lost independently of viral load and preceded the loss-of-control phase of HIV infection. By describing qualitative changes in HIV-1-specific T-cell responses that coincide with loss of viral control, we identified specific correlates of disease progression and putative markers of viral control. Our findings suggest including the markers IL-2, IFN-γ, MIP-1β, CD154 and CD45RA into monitoring of HIV-specific T-cell-responses to prospectively determine correlates of protection from disease-progression.
  Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 07/2012; 55(2):114-20. · 3.12 Impact Factor
• Source

  Available from: Silvia Heltai

  Article: Nef-specific CD45RA+ CD8+ T cells secreting MIP-1beta but not IFN-gamma are associated with nonprogressive HIV-1 infection.

  Claudia J Dembek, Sarah Kutscher, Silvia Heltai, Simone Allgayer, Priscilla Biswas, Silvia Ghezzi, Elisa Vicenzi, Dieter Hoffmann, Peter Reitmeir, Giuseppe Tambussi, [......], Elena Santagostino, Thomas Vollbrecht, Frank D Goebel, Ulrike Protzer, Rika Draenert, Marco Tinelli, Guido Poli, Volker Erfle, Mauro Malnati, Antonio Cosma
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  ABSTRACT: Long-term survival of HIV-1 infected individuals is usually achieved by continuous administration of combination antiretroviral therapy (ART). An exception to this scenario is represented by HIV-1 infected nonprogressors (NP) which maintain relatively high circulating CD4+ T cells without clinical symptoms for several years in the absence of ART. Several lines of evidence indicate an important role of the T-cell response in the modulation of HIV-1 infection during the acute and chronic phase of the disease. We analyzed the functional and the differentiation phenotype of Nef- and Tat-specific CD8+ T cells in a cohort of HIV-1 infected NP in comparison to progressors, ART-treated seropositive individuals and individuals undergoing a single cycle of ART interruption. We observed that a distinctive feature of NP is the presence of Nef-specific CD45RA+ CD8+ T cells secreting MIP-1beta but not IFN-gamma. This population was present in 7 out of 11 NP. CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cells were not detected in HIV-1 infected individuals under ART or withdrawing from ART and experiencing a rebounding viral replication. In addition, we detected Nef-specific CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cells in only 1 out of 10 HIV-1 infected individuals with untreated progressive disease. The novel antigen-specific CD45RA+ IFN-gammaneg MIP-1beta+ CD8+ T cell population represents a new candidate marker of long-term natural control of HIV-1 disease progression and a relevant functional T-cell subset in the evaluation of the immune responses induced by candidate HIV-1 vaccines.
  AIDS Research and Therapy 01/2010; 7:20. · 2.54 Impact Factor
• Article: Anti-tumor CD8+ T cell immunity elicited by HIV-1-based virus-like particles incorporating HPV-16 E7 protein.

  Paola Di Bonito, Felicia Grasso, Stefania Mochi, Linda Petrone, Emanuele Fanales-Belasio, Arianna Mei, Armando Cesolini, Giuseppe Laconi, Heinke Conrad, Helga Bernhard, Claudia J Dembek, Antonio Cosma, Stefano M Santini, Caterina Lapenta, Simona Donati, Claudia Muratori, Colomba Giorgi, Maurizio Federico
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  ABSTRACT: Here we report a novel strategy for the induction of CD8(+) T cell adaptive immune response against viral and tumor antigens. This approach relies on high levels of incorporation in HIV-1 VLPs of a mutant of HIV-1 Nef (Nef(mut)) which can act as anchoring element for foreign proteins. By in vitro assay, we found that VLP-associated Nef(mut) is efficiently cross-presented by antigen presenting cells. Inoculation in mice of VLPs incorporating the HPV-16 E7 protein fused to Nef(mut) led to an anti-E7 CD8(+) T cell response much stronger than that elicited by E7 recombinant protein inoculated with incomplete Freund's adjuvant and correlating with well-detectable anti-E7 CTL activity. Most relevantly, mice immunized with Nef(mut)-E7 VLPs developed a protective immune response against tumors induced by E7 expressing tumor cells. These results make Nef(mut) VLPs a promising candidate for new vaccine strategies focused on the induction of CD8(+) T cell immunity.
  Virology 10/2009; 395(1):45-55. · 3.35 Impact Factor