Targeting Fel d 1 to FcγRI induces a novel variation of the TH2 response in subjects with cat allergy

Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, VA 22908-1355, USA.
The Journal of allergy and clinical immunology (Impact Factor: 11.48). 04/2008; 121(3):756-762.e4. DOI: 10.1016/j.jaci.2007.10.016
Source: PubMed


Induction of CD4+ T cells that produce IL-10 or IFN-gamma is central to the protective effects of conventional allergen immunotherapy.
We examined the T-cell modulatory capacity of a fusion protein (H22-Fel d 1) that targets Fel d 1 to the high-affinity IgG receptor (FcgammaRI) on antigen-presenting cells.
Monocyte-derived dendritic cells pulsed with H22-Fel d 1 were analyzed for surface phenotype and cytokine secretion by flow cytometry and cytometric bead assay, respectively. CD4+ T cells generated after coculture with H22-Fel d 1-pulsed dendritic cells were analyzed at the single-cell level by flow cytometry after intracellular cytokine staining. The T-cell repertoire was compared for subjects with (IgE+) and without cat allergy (IgE(neg)IgG(neg)), including subjects with a modified T(H)2 response (IgE(neg)IgG+).
H22-Fel d 1 induced a semimature phenotype in dendritic cells in conjunction with a selective increase in IL-5+ and IL-10+ CD4+ T cells compared with nonreceptor-targeted Fel d 1. Amplified T cells included diverse subtypes characteristic of T(H)0 (IL-5+IFN-gamma+), regulatory T(H)1 (IL-10+IFN-gamma+) and regulatory T(H)2 (IL-10+IL-5+ cells. T-cell qualitative changes were restricted to subjects with allergy and were distinct from a modified T(H)2 response. Blocking IL-10 induced by H22-Fel d 1 selectively increased IL-5+ CD4+ T cells, suggesting that T(H)2 responses were controlled.
Targeting Fel d 1 to FcgammaRI induces a novel variation of the T(H)2 response that incorporates major elements of a protective T-cell response.

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