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

Vaccine. 2010 Feb 3;28(5):1226-33. doi: 10.1016/j.vaccine.2009.11.021. Epub 2009 Nov 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antigens / biosynthesis
  • Antigens / genetics
  • Antigens / immunology
  • Antigens, CD / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Movement / immunology
  • Cell Proliferation*
  • Cervix Uteri / immunology*
  • Cervix Uteri / metabolism
  • Female
  • Intestinal Mucosa / metabolism
  • Intestines / immunology*
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Mice
  • Mice, Transgenic
  • Spleen / immunology
  • Spleen / metabolism
  • Streptococcus gordonii / genetics
  • Streptococcus gordonii / immunology*
  • Streptococcus gordonii / metabolism
  • Time Factors

Substances

  • Antigens
  • Antigens, CD