Dendritic cells genetically engineered to express IL-10 induce long-lasting antigen-specific tolerance in experimental asthma.

Henry E, Desmet CJ, Garzé V, Fiévez L, Bedoret D, Heirman C, Faisca P, Jaspar FJ, Gosset P, Jacquet AP, Desmecht D, Thielemans K, Lekeux P, Moser M, Bureau F.
J Immunol. 2008 Nov 15;181(10):7230-42.

Dendritic cells (DCs) are professional APCs that have a unique capacity to initiate primary immune responses, including tolerogenic responses. We have genetically engineered bone marrow-derived DCs to express the immunosuppressive cytokine IL-10 and tested the ability of these cells to control experimental asthma. A single intratracheal injection of OVA-pulsed IL-10-transduced DCs (OVA-IL-10-DCs) to naive mice before OVA sensitization and challenge prevented all of the cardinal features of airway allergy, namely, eosinophilic airway inflammation, airway hyperreactivity, and production of mucus, Ag-specific Igs, and IL-4. OVA-IL-10-DCs also reversed established experimental asthma and had long-lasting and Ag-specific effects. We furthermore showed, by using IL-10-deficient mice, that host IL-10 is required for mediating the immunomodulatory effects of OVA-IL-10-DCs and demonstrated a significant increase in the percentage of OVA-specific CD4(+)CD25(+)Foxp3(+)IL-10(+) regulatory T cells in the mediastinal lymph nodes of OVA-IL-10-DC-injected mice. Finally, adoptive transfer of CD4(+) mediastinal lymph node T cells from mice injected with OVA-IL-10-DCs protected OVA-sensitized recipients from airway eosinophilia upon OVA provocation. Our study describes a promising strategy to induce long-lasting Ag-specific tolerance in airway allergy.

URL: http://www.jimmunol.org/cgi/content/full/181/10/7230

Pub Med: http://www.ncbi.nlm.nih.gov/pubmed/18981145

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