Mechanisms of allergy and clinical immunology: Targeting Fel d 1 to Fc gamma RI induces a novel variation of the TH2 response in subjects with cat allergy

• Published in: Journal of allergy and clinical immunology 2008-03, Vol.121 (3), p.756-762.e4
• Main Authors: Hulse, Kathryn E, Reefer, Amanda J, Engelhard, Victor H, Satinover, Shama M, Patrie, James T, Chapman, Martin D, Woodfolk, Judith A
• Format: Article
• Language: English
• ISSN: 0091-6749
• DOI: 10.1016/j.jaci.2007.10.016

Background: Induction of CD4+ T cells that produce IL-10 or IFN-? is central to the protective effects of conventional allergen immunotherapy. Objective: We examined the T-cell modulatory capacity of a fusion protein (H22Fel d 1) that targets Fel d 1 to the high-affinity IgG receptor (Fc?RI) on antigen-presenting cells. Methods: Monocyte-derived dendritic cells pulsed with H22Fel 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 H22Fel d 1pulsed 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 (IgEnegIgGneg), including subjects with a modified TH2 response (IgEnegIgG+). Results: H22Fel 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 TH0 (IL-5+IFN-?+), regulatory TH1 (IL-10+IFN-?+) and regulatory TH2 (IL-10+IL-5+) cells. T-cell qualitative changes were restricted to subjects with allergy and were distinct from a modified TH2 response. Blocking IL-10 induced by H22Fel d 1 selectively increased IL-5+ CD4+ T cells, suggesting that TH2 responses were controlled. Conclusion: Targeting Fel d 1 to Fc?RI induces a novel variation of the TH2 response that incorporates major elements of a protective T-cell response.