Subcutaneous allergen immunotherapy restores human dendritic cell innate immune function

Jody R Tversky, A. P. Bieneman, K. L. Chichester, Robert G Hamilton, John Thomas Schroeder

Research output: Contribution to journalArticle

Abstract

Summary Background We recently reported that human blood dendritic cells from allergic subjects have impaired IFN-α production following toll-like receptor 9 (TLR9)-dependent innate immune stimulation. It is not known how subcutaneous allergen immunotherapy (SCIT) affects dendritic cell immune responses. Objective The aim of this study is to determine how SCIT affects human dendritic cell function. Methods Peripheral blood mononuclear cell (PBMC) and plasmacytoid dendritic cells (pDCs) were isolated from the blood of seven dust mite allergic subjects at baseline and upon reaching a standard SCIT maintenance dose that included dust mite and other aeroallergens. Cells were stimulated with various adaptive and innate immune receptor stimuli, or media alone for 20 h with secreted cytokine levels determined by ELISA. A portion of the cells were used to measure intracellular signalling proteins by flow cytometry. Humoral immune responses were measured from plasma. Results SCIT resulted in a threefold increase in PBMC production of IFN-α in response to CpG at 100 nm (P=0.015) and at 500 nm (P=0.015), n=7. The predominant cell type known to produce IFN-α in response to CpG (CpG ODN-2216) and other TLR9 agonists is the pDC. As expected, a robust innate immune response from isolated pDCs was re-established among allergic subjects undergoing SCIT resulting in a fivefold increase in IFN-α production in response to CpG at 500 nm (P=0.046), n=7. In contrast, IL-6 production was unaffected by SCIT (P=0.468). Consistent with published reports, IgG4 blocking antibody increased 10-fold with SCIT (P=0.031), n=7. There was no significant increase in the frequency of pDCs or the expression of TLR9 that would account for the rise in IFN-α production. Conclusions Allergen immunotherapy increases dendritic cell TLR9-mediated innate immune function, which has previously been shown to be impaired at baseline in allergic subjects.

Original languageEnglish (US)
Pages (from-to)94-102
Number of pages9
JournalClinical and Experimental Allergy
Volume40
Issue number1
DOIs
StatePublished - Jan 2010

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Immunologic Desensitization
Dendritic Cells
Toll-Like Receptor 9
Blood Cells
Mites
Dust
Intracellular Signaling Peptides and Proteins
Blocking Antibodies
Humoral Immunity
Innate Immunity
Interleukin-6
Flow Cytometry
Immunoglobulin G
Enzyme-Linked Immunosorbent Assay
Cytokines

Keywords

  • Allergy
  • Cytokines
  • Dendritic cell
  • IFN-α
  • Immunotherapy mechanisms
  • PDC
  • SCIT
  • TLR9

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Subcutaneous allergen immunotherapy restores human dendritic cell innate immune function. / Tversky, Jody R; Bieneman, A. P.; Chichester, K. L.; Hamilton, Robert G; Schroeder, John Thomas.

In: Clinical and Experimental Allergy, Vol. 40, No. 1, 01.2010, p. 94-102.

Research output: Contribution to journalArticle

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N2 - Summary Background We recently reported that human blood dendritic cells from allergic subjects have impaired IFN-α production following toll-like receptor 9 (TLR9)-dependent innate immune stimulation. It is not known how subcutaneous allergen immunotherapy (SCIT) affects dendritic cell immune responses. Objective The aim of this study is to determine how SCIT affects human dendritic cell function. Methods Peripheral blood mononuclear cell (PBMC) and plasmacytoid dendritic cells (pDCs) were isolated from the blood of seven dust mite allergic subjects at baseline and upon reaching a standard SCIT maintenance dose that included dust mite and other aeroallergens. Cells were stimulated with various adaptive and innate immune receptor stimuli, or media alone for 20 h with secreted cytokine levels determined by ELISA. A portion of the cells were used to measure intracellular signalling proteins by flow cytometry. Humoral immune responses were measured from plasma. Results SCIT resulted in a threefold increase in PBMC production of IFN-α in response to CpG at 100 nm (P=0.015) and at 500 nm (P=0.015), n=7. The predominant cell type known to produce IFN-α in response to CpG (CpG ODN-2216) and other TLR9 agonists is the pDC. As expected, a robust innate immune response from isolated pDCs was re-established among allergic subjects undergoing SCIT resulting in a fivefold increase in IFN-α production in response to CpG at 500 nm (P=0.046), n=7. In contrast, IL-6 production was unaffected by SCIT (P=0.468). Consistent with published reports, IgG4 blocking antibody increased 10-fold with SCIT (P=0.031), n=7. There was no significant increase in the frequency of pDCs or the expression of TLR9 that would account for the rise in IFN-α production. Conclusions Allergen immunotherapy increases dendritic cell TLR9-mediated innate immune function, which has previously been shown to be impaired at baseline in allergic subjects.

AB - Summary Background We recently reported that human blood dendritic cells from allergic subjects have impaired IFN-α production following toll-like receptor 9 (TLR9)-dependent innate immune stimulation. It is not known how subcutaneous allergen immunotherapy (SCIT) affects dendritic cell immune responses. Objective The aim of this study is to determine how SCIT affects human dendritic cell function. Methods Peripheral blood mononuclear cell (PBMC) and plasmacytoid dendritic cells (pDCs) were isolated from the blood of seven dust mite allergic subjects at baseline and upon reaching a standard SCIT maintenance dose that included dust mite and other aeroallergens. Cells were stimulated with various adaptive and innate immune receptor stimuli, or media alone for 20 h with secreted cytokine levels determined by ELISA. A portion of the cells were used to measure intracellular signalling proteins by flow cytometry. Humoral immune responses were measured from plasma. Results SCIT resulted in a threefold increase in PBMC production of IFN-α in response to CpG at 100 nm (P=0.015) and at 500 nm (P=0.015), n=7. The predominant cell type known to produce IFN-α in response to CpG (CpG ODN-2216) and other TLR9 agonists is the pDC. As expected, a robust innate immune response from isolated pDCs was re-established among allergic subjects undergoing SCIT resulting in a fivefold increase in IFN-α production in response to CpG at 500 nm (P=0.046), n=7. In contrast, IL-6 production was unaffected by SCIT (P=0.468). Consistent with published reports, IgG4 blocking antibody increased 10-fold with SCIT (P=0.031), n=7. There was no significant increase in the frequency of pDCs or the expression of TLR9 that would account for the rise in IFN-α production. Conclusions Allergen immunotherapy increases dendritic cell TLR9-mediated innate immune function, which has previously been shown to be impaired at baseline in allergic subjects.

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