Targeting Fel d 1 to FcγRI induces a novel variation of the T_H2 response in subjects with cat allergy

Background: Induction of CD4⁺ T cells that produce IL-10 or IFN-γ is central to the protective effects of conventional allergen immunotherapy. Objective: 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 (FcγRI) on antigen-presenting cells. Methods: 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^negIgG^neg), including subjects with a modified T_H2 response (IgE^negIgG⁺). Results: 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_H0 (IL-5⁺IFN-γ⁺), regulatory T_H1 (IL-10⁺IFN-γ⁺) and regulatory T_H2 (IL-10⁺IL-5⁺) cells. T-cell qualitative changes were restricted to subjects with allergy and were distinct from a modified T_H2 response. Blocking IL-10 induced by H22-Fel d 1 selectively increased IL-5⁺ CD4⁺ T cells, suggesting that T_H2 responses were controlled. Conclusion: Targeting Fel d 1 to FcγRI induces a novel variation of the T_H2 response that incorporates major elements of a protective T-cell response.