Exploring the roles and plasticity of T-cell respo.. (T-BAC)
Exploring the roles and plasticity of T-cell responses in anti-BACterial immunity
Start date: May 1, 2013,
End date: Apr 30, 2015
"Antibodies against bacterial polysaccharides and proteins play a role in anti-bacterial immunity. To date, S. aureus vaccine candidates were selected to induce functional antibody responses. However, a potential role for T-cell mediated immunity is emerging, supported by the fact that impaired Th17 responses in patients with hyper IgE syndrome are linked to abnormal susceptibility to S. aureus infections. Thus, the capacity to induce specific T cell responses may be an important criterion to select vaccine antigens. Understanding the nature of anti-bacterial T cells and their behavior in steady state or under inflammatory conditions (eg, immunization) is thus important for the design of novel vaccine strategies against bacterial pathogens. Among CD4 T cells, Th17 cells play a pivotal role in mucosal host protection. These cells are mainly characterized by the production of the cytokine IL 17A but display considerable phenotypic plasticity. For S. aureus-specific Th17 cells, published data suggest a link between Th17 plasticity and the innate cytokine IL-1b, highlighting the need to better understand the functional role of the different Th17 subsets. Using S. aureus as a model, and hypothesizing that the functional profiles of CD4 T cells (Th1, Th17) may be linked to selected bacterial proteins, we first aim to identify specific S. aureus antigens with defined Th profiles in humans. Second, using in vitro stimulation methods, we aim to phenotypically characterize S. aureus-specific CD4 T cell responses induced by these proteins. Phenotypic plasticity and behavior will be studied under inflammatory (IL-1b, IL-6 or IL-23) cell culture conditions. Third, we aim to evaluate the impact of vaccination on the frequency, phenotype and plasticity of specific memory CD4 T cells, using samples from an S. aureus vaccine trial. This allows studying the phenotypes of antigen-specific CD4 T cells after in vivo exposure (vaccination) to antigens."
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