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) |
|---|---|
| Journal | Journal of Allergy and Clinical Immunology |
| Volume | 121 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jan 1 2008 |
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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
}
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 journal › Article
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
UR - http://www.scopus.com/inward/record.url?scp=40049106525&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=40049106525&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2007.10.016
DO - 10.1016/j.jaci.2007.10.016
M3 - Article
VL - 121
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 3
ER -