Intranasal immunization with vaccine vector Streptococcus gordonii elicits primed CD4+ and CD8+ T cells in the genital and intestinal tracts.
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.
Ciabattini
Annalisa
A
Laboratorio di Microbiologia Molecolare e Biotecnologia (LA.M.M.B.), Dipartimento di Biologia Molecolare, Università di Siena, 53100 Siena, Italy.
Pettini
Elena
E
Arsenijevic
Slavica
S
Pozzi
Gianni
G
Medaglini
Donata
D
D000281:Administration, Intranasal; D000818:Animals; D000941:Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D002584:Cervix Uteri / Q000276:immunology* / Q000378:metabolism; D005260:Female; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D054773:Streptococcus gordonii / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D000941:Antigens; D015703:Antigens, CD