I show a new development results of the mechanisms of nasal vaccine system in this report supported by Grand-in-Aid for Scientific Research (C) (1999 - 2001) of Japan Society for the Promotion of Science as following.
1) Nasal Vaccine: Nasal vaccination with purified P. gingivalis fimbriae and cholera toxin (CT) is an effective immunization regimen for the induction of Ag-specific Thl and Th2 cell-derive IgA immune responses that possess the ability to inhibit bacterial attachment to epithelial cells. In addition, nasal recombinant BCG vector-based vaccine can secrete the V3 principal neutralizing epitope of HIV in serum, but not mucosal secreted IgA.
2) IgA producing mucosal B-l cell: IgA-committed (sIgA^+) B-l cells mainly resided in the lamina propria in the nasal cavity, while sIgA^+ B-2 cell formed in mucosal inductive site such as nasal associated lymphoid tissue. IL-5/IL-5R signaling pathway is important for the development of common mucosal immune system independent sIgA^+ B-l cell in nasal cavity in vivo. Further, IL-15 is also important cytokine for the differentiation of both sIgM^+, IgA- and slgM^-, sIgA^+ B-1 cells expressing IL-15R into IgA-producing cells in mucosal tissues. NALT is considered to be an important inductive site for the induction of antigen-specific mucosal and systemic immunity against nasally-administered vaccine antigen.
3) Organization of NALT: When LTα^<-/->, IL7-R^<-/-> and aly/aly mice were examined, known to lacking PLN and/or PP, NALT was observed in nasal cavity. Further, NALT like structure was also found in PP null mice generated by in vivo treatments with anti-IL7R mAb and LTβR-Ig. These findings suggested that NALT organogenesis is independently operated from a group of known lymphoid tissue generation cytokine signaling pathway.