Antigen-bearing dendritic cells from the sublingual mucosa recirculate to distant systemic lymphoid organs to prime mucosal CD8 T cells

Abstract

Effector T cells are described to be primed in the lymph nodes draining the site of immunization and to recirculate to effector sites. Sublingual immunization generates effector T cells able to disseminate to the genital tract. Herein, we report an alternative mechanism that involves the recirculation of antigen-bearing dendritic cells (DCs) in remote lymphoid organs to prime T cells. Sublingual immunization with a muco-adhesive model antigen unable to diffuse through lymphatic or blood vessels induced genital CD8 T cells. The sublingual draining lymph nodes were not mandatory to generate these lymphocytes, and antigen-bearing DCs from distant lymph nodes and spleen were able to prime specific CD8 T cells in a time- and dose-dependent manner. This study demonstrates, for the first time, that antigen-bearing DCs originating from the site of immunization recirculate to distant lymphoid organs and provides insights into the mechanism of distant CD8 T-cell generation by sublingual immunization.

Mucosal vaccine delivery: Current state and a pediatric perspective

“…Antigen-loaded DCs drain from the sublingual mucosa to local lymph nodes where they prime both B and T lymphocytes. The activated lymphocytes can then leave the site of antigen presentation, enter blood circulation and seed other selected mucosal sites where they can regulate differentiation and maturation of B and T (Th1 & Th2) cells [69]. Figure 4C provides a cartoon representation of the oral cavity as a route of vaccine delivery and summarizes the major delivery barriers.…”

Resident Memory T Cells as Surrogate Markers of the Efficacy of Cancer Vaccines

“…We and other authors have shown that the mucosal route of immunization imprints T cells with a mucosal homing program defined by a profile of integrin and chemokine receptors promoting their homing to the site of initial activation. Tumors located at mucosal sites (lung, colorectal, genital, head and neck) are exposed to mucosal immunity, organized within a connecting network called MALT (mucosal-associated lymphoid tissues), which may explain why the intranasal route of immunization may induce a genital immune response via the recirculation of mucosal dendritic cells (12). In the study by Sun and colleagues, a4b7 and CCR9 induced on T cells are necessary for the homing of antitumor-specific T cells to the cervicovaginal tract (1).…”

Mucosal vaccines

“…65,66 Indeed, DCs activated at a particular immunization site, recirculate to distant lymphoid organs and induce distant T cell priming, explaining the genital immune response observed after i.n immunization with the B subunit of cholera toxin (CTB) coupled to OVA. 67 In clinical settings, however, an intravaginal boost was required to attract T cells to the genital tract after i.n immunization with the cholera toxin coupled to OVA. 68 Additionally, oral, nasal or intravaginal immunization with CTB were able to induce comparable secreted IgA levels in the vaginal tract but no cellular immune responses.…”