Naïve CD4⁺ T Cell Activation in the Nasal-Associated Lymphoid Tissue following Intranasal Immunization with a Flagellin-Based Subunit Vaccine

The nasal-associated lymphoid tissues (NALT) are generally accepted as an immune induction site, but the activation of naïve T-cells in that compartment has not been well-characterized. I wanted to determine if early events in naïve CD4⁺ T cell activation and the extent of antigen specific cell division are similar in NALT to that observed in other secondary lymphoid compartments. I performed antigen tracking experiments and analyzed the activation of naïve antigen-specific CD4⁺ T cells in the nasal-associated lymphoid tissues (NALT). I directly observed transepithelial transport of fluorescently labeled antigen from the lumen of the airway to the interior of the NALT two hours following immunization. One day following intranasal (i.n.) immunization with antigen and adjuvant, antigen-specific CD4⁺ T cells in the NALT associated as clusters, while antigen-specific CD4⁺ T cells in control mice immunized with adjuvant only remained dispersed. The antigen-specific CD4⁺ populations in the NALT and cranial deep cervical lymph nodes of immunized mice expanded significantly by day three following immunization. These findings are consistent with initial activation of naïve CD4⁺ T cells in the NALT and offer insight into adjuvant mechanism of flagellin in the upper respiratory compartment.