Differential capacity of CD8α+ or CD8α dendritic cell subsets to prime for eosinophilic airway inflammation in the T-helper type 2-prone milieu of the lung

Authors


Bart N. Lambrecht, Department of Pulmonary Medicine, Room Ee2251, Erasmus Medical Center, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. E-mail: b.lambrecht@erasmusmc.nl

Summary

Background Different subsets of dendritic cells (DCs), identified in mouse spleen by their differential expression of CD8α, can induce different T-helper (Th) responses after systemic administration. CD8α DCs have been shown to preferentially induce Th type 2 (Th2) responses whereas CD8α+ DCs induce Th1 responses.

Objective To study if these DC subsets can still induce different Th responses in the Th2-prone milieu of the lung and differentially prime for eosinophilic airway inflammation, typical of asthma.

Methods Donor mice first received daily Flt3L injections to expand DC numbers. Purified CD8α+ or CD8α splenic DCs were pulsed with ovalbumin (OVA) or phosphate-buffered saline and injected intratracheally into recipient mice in which carboxyfluorescein diacetate succinimidyl ester-labelled OVA-specific T cell receptor transgenic T cells had been injected intravenously 2 days earlier. T cell proliferation and cytokine production of Ag-specific T cells were evaluated in the mediastinal lymph nodes (MLNs) 4 days later. The capacity of both subsets of DCs, to prime for eosinophilic airway inflammation was determined by challenging the mice with OVA aerosol 10 days later.

Results CD8α DCs migrated to the MLN and induced a vigorous proliferative T cell response accompanied by high-level production of IL-4, IL-5, IL-10 and also IFN-γ during the primary response and during challenge with aerosol, leading to eosinophilic airway inflammation. In the absence of migration to the MLN, CD8α+ DCs still induced a proliferative response with identical levels of IFN-γ but reduced Th2 cytokines compared with CD8α DCs, which led to weak eosinophilic airway inflammation upon OVA aerosol challenge. Unpulsed DCs did not induce proliferation or cytokine production in Ag-specific T cells.

Conclusion CD8α DCs are superior compared with CD8α+ DCs in inducing Th2 responses and eosinophilic airway inflammation in the Th2-prone environment of the lung.

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