Vaginal (type-II) mucosa acts as an inductive site during the generation of primary CD8+ T cell mucosal immune responses (P3186)

It is widely believed that primary immune induction in type-II mucosa (vagina, mouth & cornea) occurs in the draining LNs due to a lack of mucosa-associated lymphoid tissue. In this process, naïve T cells located in the draining LNs are primed by antigen (Ag)-bearing dendritic cells migrating from the Ag-exposed mucosa. Primed T cells then travel to the mucosal site through the bloodstream. In contrast to this paradigm, we show that vaginal mucosa itself can act as an immune inductive site for generation of primary CD8+ T cell mucosal immunity. As evidence, we found that naïve CD8+ T cells routinely migrated to the female reproductive tract and that Ag-specific CD8+ T cells could be generated in the LN-deficient mice after intravaginal immunization. Further, the adoptively transferred naïve OT-1 CD8+ T cells were activated in the vaginal mucosa but not in the draining LNs at 24 hours after intravaginal immunization, even in the presence of FTY720, a drug blocking the egress of T cells from LNs. In addition, the Ag-bearing cells isolated from immunized vaginal mucosa were able to stimulate naïve TCR-transgenic RT-1 CD8+ T cells to secret IFN-γ and undergo proliferation. Finally, vaginal mucosa largely supported the expansion of Ag-specific CD8+ T cells. In conclusion, we present evidence for a new paradigm for primary CD8+ T cell immune induction in type-II mucosa of the vagina, one that occurs locally without the help of draining LNs or mucosa-associated lymphoid tissue.