High Frequency of CD4 super(+) T Cells Specific for the TB10.4 Protein Correlates with Protection against Mycobacterium tuberculosis Infection

TB10.4 is a newly identified antigen of Mycobacterium tuberculosis recognized by human and murine T cells upon mycobacterial infection. Here, we show that immunization with Mycobacterium bovis BCG induces a strong, genetically controlled, Th1 immune response against TB10.4 in mice. BALB/c and C57BL/...

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Bibliographic Details
Published in:Infection and immunity 2006-06, Vol.74 (6), p.3396-3407
Main Authors: Hervas-Stubbs, Sandra, Majlessi, Laleh, Simsova, Marcela, Morova, Jana, Rojas, Marie-Jesus, Nouze, Clemence, Brodin, Priscille, Sebo, Peter, Leclerc, Claude
Format: Article
Language:English
Subjects:
Bordetella pertussis
Mycobacterium bovis
Mycobacterium tuberculosis
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Summary:TB10.4 is a newly identified antigen of Mycobacterium tuberculosis recognized by human and murine T cells upon mycobacterial infection. Here, we show that immunization with Mycobacterium bovis BCG induces a strong, genetically controlled, Th1 immune response against TB10.4 in mice. BALB/c and C57BL/6 strains behave as high and low responders to TB10.4 protein, respectively. The TB10.4:74-88 peptide was identified as an immunodominant CD4 super(+) T-cell epitope for H-2 super(d) mice. Since recent results, as well as the present study, have raised interest in TB10.4 as a subunit vaccine, we analyzed immune responses induced by this antigen delivered by a new vector, the adenylate cyclase (CyaA) of Bordetella pertussis. CyaA is able to target dendritic cells and to deliver CD4 super(+) or CD8 super(+) T-cell epitopes to the major histocompatibility complex class II/I molecule presentation pathways, triggering specific Th1 or cytotoxic T-lymphocyte (CTL) responses. Several CyaA harboring either the entire TB10.4 protein or various subfragments containing the TB10.4:20-28 CTL epitope were shown to induce TB10.4-specific Th1 CD4 super(+) and CD8 super(+) T-cell responses. However, none of the recombinant CyaA, injected in the absence of adjuvant, was able to induce protection against M. tuberculosis infection. In contrast, TB10.4 protein administered with a cocktail of strong adjuvants that triggered a strong Th1 CD4 super(+) T-cell response induced significant protection against M. tuberculosis challenge. These results confirm the potential value of the TB10.4 protein as a candidate vaccine and show that the presence of high frequencies of CD4 super(+) T cells specific to this strong immunogen correlates with protection against M. tuberculosis infection.
ISSN:0019-9567
1098-5522