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Matthieu Perreau,
Virginie Rozot, Hugh C Welles,
Felicitas Belluti-Enders,
Selena Vigano,
Michel Maillard,
Gian Dorta,
Jesica Mazza-Stalder,
Pierre-Alexandre Bart,
Thierry Roger,
Thierry Calandra,
Laurent Nicod,
Alexandre Harari
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ABSTRACT: Protective immunity to Mycobacterium tuberculosis (Mtb) is commonly ascribed to a Th1 profile; however, the involvement of Th17 cells remains to be clarified. Here, we characterized Mtb-specific CD4+ T cells in blood and bronchoalveolar lavages (BALs) from untreated subjects with either active tuberculosis disease (TB) or latent Mtb infection (LTBI), considered as prototypic models of uncontrolled or controlled infection, respectively. The production of IL-17A, IFN-γ, TNF-α, and IL-2 by Mtb-specific CD4+ T cells was assessed both directly ex vivo and following in vitro antigen-specific T-cell expansion. Unlike for extracellular bacteria, Mtb-specific CD4+ T-cell responses lacked immediate ex vivo IL-17A effector function in both LTBI and TB individuals. Furthermore, Mtb-specific Th17 cells were absent in BALs, while extracellular bacteria-specific Th17 cells were identified in gut biopsies of healthy individuals. Interestingly, only Mtb-specific CD4+ T cells from 50% of LTBI but not from TB subjects acquired the ability to produce IL-17A following Mtb-specific T-cell expansion. Finally, IL-17A acquisition by Mtb-specific CD4+ T cells correlated with the coexpression of CXCR3 and CCR6, currently associated to Th1 or Th17 profiles, respectively. Our data demonstrate that Mtb-specific Th17 cells are selectively undetectable in peripheral blood and BALs from TB patients.
European Journal of Immunology 02/2013; · 5.10 Impact Factor
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Matthieu Perreau, Hugh C Welles,
Celine Pellaton,
Bebeka Gjoksi,
Lambert Potin,
Ricardo Martin,
Alexandre Harari,
Andrew Bett,
Danilo Casimiro,
Jason Gall,
Dan H Barouch,
Eric J Kremer,
Giuseppe Pantaleo
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ABSTRACT: Adenovirus serotype 5 (Ad5) vectors and specific neutralizing antibodies (NAbs) generate immune complexes (ICs) which are potent inducers of dendritic cell (DC) maturation. Here we show that ICs generated with rare Ad vector serotypes, such as Ad26 and Ad35, which are lead candidates in HIV vaccine development, are poor inducers of DC maturation and that their potency in inducing DC maturation strongly correlated with the number of Toll-like receptor 9 (TLR9)-agonist motifs present in the Ad vector's genome. In addition, we showed that antihexon but not antifiber antibodies are responsible for the induction of Ad IC-mediated DC maturation.
Journal of Virology 04/2012; 86(11):6279-85. · 5.40 Impact Factor
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ABSTRACT: Dendritic cells (DCs) are the most potent type of antigen presenting cell (APC) to stimulate T cells [1, 2]. However, the modulation of antigen-specific T-cell responses against a variety of pathogens using different types of APCs such as DCs and monocytes has never been systematically compared. We have therefore performed a comprehensive analysis of the quantity and quality of memory CD4+ T-cell responses directed against a variety of antigens including peptide, protein, viral, fungal and bacterial derived-antigens following stimulation with antigen-loaded DCs or monocytes.
European Journal of Immunology 12/2011; 42(3):799-802. · 5.10 Impact Factor
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Matthieu Perreau, Hugh C Welles,
Alexandre Harari,
Olivia Hall,
Ricardo Martin,
Michel Maillard,
Gian Dorta,
Pierre-Alexandre Bart,
Eric J Kremer,
Jim Tartaglia,
Ralf Wagner,
Mariano Esteban,
Yves Levy,
Giuseppe Pantaleo
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ABSTRACT: In the present study, we have investigated the anatomic distribution in blood and gut mucosal tissues of memory poxvirus-specific CD4 and CD8 T cells in subjects vaccinated with smallpox and compared it with vector (NYVAC)-specific and HIV insert-specific T-cell responses induced by an experimental DNA-C/ NYVAC-C vaccine regimen. Smallpox-specific CD4 T-cell responses were present in the blood of 52% of the subjects studied, while smallpox-specific CD8 T cells were rarely detected (12%). With one exception, smallpox-specific T cells were not measurable in gut tissues. Interestingly, NYVAC vector-specific and HIV-specific CD4 and CD8 T-cell responses were detected in almost 100% of the subjects immunized with DNA-C/NYVAC-C in blood and gut tissues. The large majority (83%) of NYVAC-specific CD4 T cells expressed α4β7 integrins and the HIV coreceptor CCR5. These results demonstrate that the experimental DNA-C/NYVAC-C HIV vaccine regimen induces the homing of potentially protective HIV-specific CD4 and CD8 T cells in the gut, the port of entry of HIV and one of the major sites for HIV spreading and the depletion of CD4 T cells.
Journal of Virology 07/2011; 85(19):9854-62. · 5.40 Impact Factor
