4.5 Article

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

Journal

VACCINE
Volume 28, Issue 5, Pages 1226-1233

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2009.11.021

Keywords

T cell priming; Mucosal vaccines; Vaccine vectors; Streptococcus gordonii

Funding

  1. Commission of the European Communities, Sixth Framework Programme [LSHP-Cr-2003-503240]
  2. Mucosal Vaccines for Poverty-Related Diseases (MUVAPRED)
  3. European Vaccines and Microbicides Enterprise (EUROPRISE) [037611]
  4. Istituto Superiore di Sanita [45G.27]

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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. (C) 2009 Elsevier Ltd. All rights reserved.

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