T-cell receptor repertoire diversity during persistent and fatal ehrlichial infections (40.17)

Abstract

Abstract Human monocytotropic ehrlichiosis (HME), an emerging tick-transmitted bacterial disease, is caused by Ehrlichia chaffeensis. HME is modeled in C57BL/6 mice using Ehrlichia muris, which causes persistent infection, and Ixodes ovatus Ehrlichia (IOE), which is either acutely lethal or sub-lethal depending on the dose and route of inoculation. To better define the roles of T cells in protection and pathogenesis, we analyzed TCR Vβ usage in activated T cells from mice infected with E. muris or IOE by TCR-CDR3 spectratyping. Our data indicated that E. muris, but not IOE, induced oligoclonal expansion of CD4+ T cells within the several Vβ families (Vβ1, Vβ2, Vβ8.1, Vβ8.2, Vβ12, Vβ16 and Vβ19) early during the effector phase of T cell response. Further, oligoclonal expansion of CD8+ T cells within the Vβ8.2, Vβ4 and Vβ19 families was observed during E. muris infection compared to oligoclonal expansion of Vβ16 and Vβ19 CD8+ T cells in mice infected with IOE. Functional analysis of T cell subsets by flow cytometry indicated that E. muris induced a strong Th1 response involving several Vβ families compared to a weak Th1 response induced by IOE. The data suggested that unlike IOE, E. muris induces a strong Th1 response which tends to focus on certain Vβ families early during the effector phase of T cell response. Future studies will focus on functional characterization of memory T cell subsets induced following infection with E. muris.