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

Kathryn E. Hulse, Amanda J. Reefer, Victor H. Engelhard, Shama M. Satinover, James T. Patrie, Martin D. Chapman, Judith A. Woodfolk*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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 languageEnglish (US)
Pages (from-to)756-762.e4
JournalJournal of Allergy and Clinical Immunology
Volume121
Issue number3
DOIs
StatePublished - 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

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