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Peripherally induced Foxp3+ regulatory T cells mediates the immunomodulatory effect of intravenous immunoglobulin in an experimental model of allergic airway disease
Allergy, Asthma & Clinical Immunology volume 10, Article number: A50 (2014)
IVIg is a polyclonal IgG preparation with potent immune-modulating properties. We demonstrated that IVIg protects against airway hyperreactivity (AHR) and airway inflammation in mouse models of allergic airway disease, accompanied by peripheral induction of Foxp3+regulatory T-cells (iTreg). The requirement of IVIg-induced iTreg and their antigen-specificity in attenuation of AHR and airway inflammation remains unknown.
We utilized DEREG mice, carrying a transgenic diphtheria toxin receptor under the control of the Foxp3 promoter, allowing for selective depletion of Foxp3+Treg by the application of diphtheria toxin (DT). Mice were sensitized and challenged with ovalbumin (OVA) and treated with IVIg. AHR was measured using a FlexiVent small animal ventilator. Total and antigen-specific IgE, as well as pro-inflammatory cytokines levels were determined in serum and alveolar lavage, using ELISA.
In the absence of Treg, due to multiple DT doses before and after the treatment, IVIg was not able to attenuate AHR, diminish IgE levels and Th-2 type cytokine production, nor alleviate airway inflammation. However, mice in which the pre-established Treg cells (nTreg) were depleted before but not following IVIg treatment demonstrated an induction of Foxp3+Treg to IVIg therapy and did not develop AHR and airway inflammation to allergen-challenge. Adoptive transfer of enriched IVIg-induced iTreg from OVA-IVIg treated mice failed to transfer protection to mice exposed to ragweed, but was protective in OVA-sensitized and challenged mice.
Treg can be induced from effector CD4+T-cells in the absence of nTreg. IVIg-induced antigen specific Treg are capable of suppressing all aspects of antigen-driven airway inflammation in an antigen-specific manner.
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Massoud, A.H., Kaufman, G., Taylor, M. et al. Peripherally induced Foxp3+ regulatory T cells mediates the immunomodulatory effect of intravenous immunoglobulin in an experimental model of allergic airway disease. All Asth Clin Immun 10, A50 (2014). https://doi.org/10.1186/1710-1492-10-S1-A50
- Treg Cell
- Airway Inflammation
- Diphtheria Toxin
- IVIg Therapy
- IVIg Treatment