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Influence of Mucosal Adjuvants on Antigen Passage and CD4⁺ T Cell Activation during the Primary Response to Airborne Allergen¹

Matthew E. Wikstrom^2,*, Eva Batanero, Miranda Smith^*, Jennifer A. Thomas^*, Christophe von Garnier^3,*, Patrick G. Holt^* and Philip A. Stumbles^2,*,

^* Telethon Institute for Child Health Research, Centre for Child Health Research and the School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia; Departamento de Bioquimica y Biologia Molecular, Universidad Complutense, Madrid, Spain; and Division of Health Sciences, Murdoch University, Perth, Western Australia

Ag delivery via the nasal route typically induces tolerance or fails to polarize CD4⁺ T cell responses unless an adjuvant is provided. To better understand this process, we assessed the effects of two mucosal adjuvants, Escherichia coli LPS and cholera toxin (CT), on Ag passage and T cell activation in the draining lymph nodes (DLN) of BALB/c mice following per nasal administration of the model protein allergen, OVA. We found a range of cell types acquired small amounts of fluorescent OVA in the DLN 4 h after per nasal administration. However, this early uptake was eclipsed by a wave of OVA⁺CD8^low dendritic cells that accumulated in the DLN over the next 20 h to become the dominant OVA-processing and -presenting population. Both LPS and CT stimulated increases in CD80 and CD86 expression on OVA⁺CD8^low DC. LPS also increased the number of OVA⁺CD8^low dendritic cells accumulating in the DLN. When the primary T cell response was examined after adoptive transfer of CD4⁺ T cells from DO11.10 mice, CT and LPS stimulated surprisingly similar effects on T cell activation and proliferation, IL-4 and IFN- priming, and memory T cell production. Despite these similarities, T cell recipients immunized with CT, but not LPS, developed lung eosinophilia upon secondary OVA challenge. Thus, we found no bias within the DLN in Ag handling or the primary T cell response associated with the eventual Th2 polarization induced by CT, and suggest that additional tissue-specific factors influence the development of allergic disease in the airways.

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