Induction of anergic allergen-specific suppressor T cells using tolerogenic dendritic cells derived from children with allergies to house dust mites

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:125

Article

Pacciani, Valentina^2,3  Gregori, Silvia³  Chini, Loredana¹  Corrente, Stefania¹  Chianca, Marco¹  Moschese, Viviana¹  Rossi, Paolo^1,2  Roncarolo, Maria Grazia^3,4  Angelini, Federica^1,2 

[1] Univ Roma Tor Vergata, Div Pediat, I-00133 Rome, Italy

[2] Bambino Gesu Pediat Hosp, Dept Pediat Med, Immuno Infectivol Unit, Rome, Italy

[3] San Raffaele Telethon Inst Gene Therapy, HSR TIGET, Milan, Italy

[4] Univ Vita Salute San Raffaele, Milan, Italy

关键词: Allergy;    dendritic cells;    Der p 2;    house dust mites;    IL-10;    T(H)2 cells;    Tr1 cells;   

DOI  :  10.1016/j.jaci.2009.12.004

来源: Elsevier

【 摘 要 】

Background: Dendritic cells (DCs) regulate the immune response to allergens in the lung; they induce either effector or regulatory T cells, which promote or suppress, respectively, the development of allergy. IL-10 is a potent immunosuppressive cytokine that induces type 1 regulatory (Tr1) T cells. Objective: To generate allergen-specific Tr1 cells in vitro from children with allergy. Methods: Monocyte-derived DCs from children with allergy to house dust mites (HDM) were generated by incubating the cells with IL-10 and pulsing them with Der p 2, a major HDM allergen, or by pulsing them with Der p 2 and incubating them with IL-10 during their last 2 days of differentiation. Results: Der p 2 specific T-cell proliferation and T(H)2 cytokine production were significantly reduced when T cells from patients with allergy to HDM were activated with autologous Der p 2 pulsed DCs that had been differentiated or incubated with IL-10. T-cell lines generated with Der p 2 pulsed DCs that were differentiated with IL-10 were hyporesponsive to reactivation with Der p 2 and able to suppress Der p 2 specific T(H)2 effector cells. Conclusion: Dendritic cells differentiated in the presence of IL-10 and pulsed with allergen gave rise to a population of tolerogenic DCs that induced allergen-specific Tr1 cells. This finding represents an important step forward to the prospective clinical application of tolerogenic DCs to modulate allergen-specific T-cell responses. (J Allergy Clin Immunol 2010;125:727-36.)

【 授权许可】

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