Mechanisms of allergy and clinical immunologyCD4+CD25+ regulatory T cells reverse established allergic airway inflammation and prevent airway remodeling
Section snippets
Mice
Female BALB/c mice were purchased from Harlan (Indianapolis, Ind). DO11.10 mice were kept in a breeding colony at the Imperial College animal facility. UK Home Office guidelines for animal welfare based on the Animals (Scientific Procedures) Act 1986 were strictly observed.
Isolation of CD4+CD25+ regulatory T cells
Ovalbumin (OVA)–specific CD4+CD25+ cells were isolated from the spleens of DO11.10 mice by using a CD4+CD25+ regulatory T-cell isolation kit according to the manufacturer's protocol (Miltenyi Biotec, Bergisch Gladbach,
Transfer of CD4+CD25+ regulatory T cells reverses existing allergen-induced inflammation
We set out to determine whether therapeutic transfer of allergen-specific CD4+CD25+ regulatory T cells could reverse existing inflammation and AHR. OVA-sensitized and challenged mice received either CD4+CD25+ regulatory T cells or an equivalent volume of PBS on day 26. In this model this represents the peak of acute inflammation before the onset of airway remodeling (see Fig E2 available in this article's Online Repository at www.jacionline.org).10 Mice were then killed after further OVA
Discussion
We have demonstrated for the first time that therapeutic transfer of allergen-specific CD4+CD25+ regulatory T cells is effective in resolving established inflammation and preventing the development of airway remodeling. However, CD4+CD25+ regulatory T-cell transfer late in a chronic challenge model had no effect on established inflammation and remodeling.
The ability of CD4+CD25+ regulatory T cells to reverse established airway inflammation and prevent development of airway remodeling is in
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Supported by the Wellcome Trust (reference no. 057704). D.S.R. was supported by a Wellcome Trust Research Leave Award for Clinical Academics, and C.M.L. was supported by a Wellcome Senior Fellowship in Basic Biomedical Sciences.
Disclosure of potential conflict of interest: J. Kearley is employed by MedImmune, Inc. D. S. Robinson has consulting arrangements with MedImmune and Leti and is on the speakers' bureau for GlaxoSmithKline. C. M. Lloyd has declared that she has no conflict of interest.