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 journalArticle

22 Citations (Scopus)

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)
JournalJournal of Allergy and Clinical Immunology
Volume121
Issue number3
DOIs
StatePublished - Jan 1 2008

Fingerprint

Hypersensitivity
Cats
T-Lymphocytes
Interleukin-10
Interleukin-5
Dendritic Cells
Flow Cytometry
Cytokines
Immunologic Desensitization
Phenotype
IgG Receptors
Antigen-Presenting Cells
Coculture Techniques
Immunoglobulin E
Monocytes
Staining and Labeling
Proteins

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

Cite this

Hulse, Kathryn E. ; Reefer, Amanda J. ; Engelhard, Victor H. ; Satinover, Shama M. ; Patrie, James T. ; Chapman, Martin D. ; Woodfolk, Judith A. / Targeting Fel d 1 to FcγRI induces a novel variation of the TH2 response in subjects with cat allergy. In: Journal of Allergy and Clinical Immunology. 2008 ; Vol. 121, No. 3.
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title = "Targeting Fel d 1 to FcγRI induces a novel variation of the TH2 response in subjects with cat allergy",
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.",
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author = "Hulse, {Kathryn E.} and Reefer, {Amanda J.} and Engelhard, {Victor H.} and Satinover, {Shama M.} and Patrie, {James T.} and Chapman, {Martin D.} and Woodfolk, {Judith A.}",
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Targeting Fel d 1 to FcγRI induces a novel variation of the TH2 response in subjects with cat allergy. / Hulse, Kathryn E.; Reefer, Amanda J.; Engelhard, Victor H.; Satinover, Shama M.; Patrie, James T.; Chapman, Martin D.; Woodfolk, Judith A.

In: Journal of Allergy and Clinical Immunology, Vol. 121, No. 3, 01.01.2008.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Targeting Fel d 1 to FcγRI induces a novel variation of the TH2 response in subjects with cat allergy

AU - Hulse, Kathryn E.

AU - Reefer, Amanda J.

AU - Engelhard, Victor H.

AU - Satinover, Shama M.

AU - Patrie, James T.

AU - Chapman, Martin D.

AU - Woodfolk, Judith A.

PY - 2008/1/1

Y1 - 2008/1/1

N2 - 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.

AB - 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.

KW - CD4 T cells

KW - CD64

KW - H22-Fel d 1

KW - IFN-γ

KW - IL-10

KW - IL-5

KW - dendritic cells

KW - immunotherapy

KW - regulatory T cells

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