Intranasal immunization with vaccine vector Streptococcus gordonii elicits primed CD4 + and CD8 + T cells in the genital and intestinal tracts

Abstract

Generation of primed T cells is crucial for the development of optimal vaccination strategies. Using a TCR-transgenic CD4 + and CD8 + T cell adoptive transfer model, we demonstrate that a single nasal immunization with recombinant Streptococcus gordonii induces antigen-specific primed T cells in lymph nodes draining the genital and intestinal tracts with about 80% of CD4 + and 50% of CD8 + proliferating cells. T cell clonal expansion was also observed in cervical lymph nodes, draining the immunization site, and in the spleen. The modulation of CD44 and CD45RB marker expression indicated that proliferating T cells were activated. Proliferation in distal mesenteric and iliac lymph nodes and in the spleen was observed 5 days after nasal immunization, while in draining cervical lymph nodes proliferation peaked already at day 3. The division profile of transgenic T cells observed in iliac and mesenteric lymph nodes was discontinuous, showing the lack of early cell divisions. The kinetics of T cell clonal expansion, the discontinuous division profile and the modulation of migration markers such as CD62L suggest that activated antigen-specific T cells disseminate from the immunization site to distal intestinal and genital tracts. These data demonstrate the efficacy of nasal immunization with recombinant S. gordonii in eliciting CD4 + and CD8 + T cell priming not only in draining sites, but also in the genital and intestinal tracts and in the spleen.