NALT CD11b+ Dendritic Cell Migration Contributes to Induction of Ag Specific Immunity (B111)

Abstract

Abstract Our previous study showed that targeting nasopharyngeal-associated lymphoreticular tissue (NALT) dendritic cells (DCs) with an adenovirus vector expressing Flt3 Ligand (Ad-FL) induced Ag-specific mucosal immunity that mediated by increased numbers of DCs and CD4+ Th1- and Th2-type cytokine responses. In this study, we examined the kinetics of DC subset formation and intracellular cytokine production in NALT and in cervical lymph nodes (CLNs). C57BL/6 mice were nasally immunized with Ad-FL and OVA three times at weekly intervals. As controls, mice were given Ad expressing the firefly luciferase protein (Ad-Luc). Mononuclear cells were isolated at various time points and the frequencies of DC subsets and intracellular cytokine production by CD4+ T cells were determined by FACS. An Increased frequency in CD11b+ DCs was seen in nasal passages (NPs) and submundibular glands (SMGs) at day 21. On the other hand, the frequency as well as the actual numbers of DCs in NALT was the highest 3 days after the second nasal immunization. Further, peak cell numbers of CD11b+ DCs in CLNs were seen at day 14. Of importance, intracellular cytokine FACS analysis showed highest IFN- γ and IL-4 production in CLNs at day14. These results suggest that NALT CD11b+ DCs migrate into NPs and SMGs via the CLN and play an important role in the induction of both Th1- and Th2-type cytokine responses in mice given Ad-FL as nassal adjuvant. Supported by DE 12242, AI 18958, AI 43197, and AG 025873.