Characterization of the CD8+ T cell response in rickettsial infections (P3330)

Abstract

Natural and experimental rickettsial infections provide strong and cross-protective immunity if the individual survives the acute infection. Although resistance to rickettsial infections is attributed to the induction of antigen-specific T cells, particularly CD8+ T cells, the characterization of the cellular immune response has not been systematically addressed. Here, we report the systematic, kinetic and ex vivo analysis of CD8+ T cells from spleen, liver, lungs and lymph nodes by flow cytometry with specific panels to address the activation, effector, and memory phases of the anti-rickettsial response in C3H/HeN mice infected with R. typhi. Our findings suggest that the instauration of the effector phase occurs around 7dpi which coincides with the rickettsial clearance. This phase was characterized by an increased frequency of CD8+ T cells with a phenotype compatible with effector cells:CD44+CD43+CD27-/+ and CD44+CD43-/+CD127-; along with an increased production of IFN-γ and GZM B. A more robust production of IFN-γ and GZM-B was detected in the target organs, highlighting the compartmentalization of the immune response. Furthermore, at 7dpi, differences in the production of IFN-γ and GZM-B between controls and mice immunized with a vaccine candidate were also observed. These findings are relevant for vaccine development, providing insights about meaningful time points and specific correlates of protection that can be used as a paradigm for anti-rickettsial vaccine testing.