Abstract
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 (IgEnegIgGneg), including subjects with a modified TH2 response (IgEnegIgG+). 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 TH0 (IL-5+IFN-γ+), regulatory TH1 (IL-10+IFN-γ+) 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 H22-Fel d 1 selectively increased IL-5+ CD4+ T cells, suggesting that TH2 responses were controlled. Conclusion: Targeting Fel d 1 to FcγRI induces a novel variation of the TH2 response that incorporates major elements of a protective T-cell response.
Original language | English (US) |
---|---|
Pages (from-to) | 756-762.e4 |
Journal | Journal of Allergy and Clinical Immunology |
Volume | 121 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2008 |
Keywords
- CD4 T cells
- CD64
- H22-Fel d 1
- IFN-γ
- IL-10
- IL-5
- dendritic cells
- immunotherapy
- regulatory T cells
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology