Monitoring antigen-specific T cell responses to B. burgdorferi 2253490

Abstract

Abstract Introduction Despite decades of research into Borrelia burgdorferi immunopathogenesis, less is known about antigen-specific T cell responses to this bacterial pathogen than the role of antibodies. Studying antigen-specific T cell responses to B. burgdorferi has been challenging due to the relatively few immunological tools available. Methods To address this, we have engineered B. burgdorferi to express a well-characterized CD4+ T cell epitope from chicken ovalbumin (Bb-OVA). Using adoptively transferred OVA-specific T cells from OT-II TCR transgenic mice, we show that these OVA-specific T cells proliferate during infection in an antigen-specific manner in response to Bb-OVA but not Bb-control. Using a variety of markers, we have characterized these antigen-specific T cells during various stages of infection, and the sites to which OVA-specific cells migrate. Results While polarization of OVA- specific T cells driven by natural infection do not provide robust protection, we show that reprograming OVA-specific T cells in vitro to different T-helper polarizations before adoptive transfer can reduce bacterial burden and immunopathology in vivo. Conclusion Taken together, our data demonstrate that although T cells are misprogrammed during natural infection, one can overcome this by reprogramming T cells towards alternative polarizations to reduce burden and immunopathology (eg. carditis and arthritis). Understanding the basis of these mechanisms is key to well-informed vaccine design that, with the help of adjuvants which can polarize T cells towards different subsets, will elicit strong T cell responses to confer long-lasting protection. Funding Source n/a Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)