Reversal of human allergen-specific CRTH2+ T(H)2 cells by IL-12 or the PS-DSP30 oligodeoxynucleotide

J Allergy Clin Immunol. 2001 Nov;108(5):815-21. doi: 10.1067/mai.2001.119156.

Abstract

Background: The chemoattractant receptor homologous molecule expressed on T(H)2 cells (CRTH2) is a receptor for prostaglandin D(2), which among human T cells is selectively expressed by T(H)2 and type 2 cytotoxic effectors.

Objective: Our purpose was to assess whether the cytokine production profile of T(H)2 effectors could be reversed by exploiting their selective expression of CRTH2.

Methods: CRTH2(+) T cells were purified from the blood of allergic subjects, stimulated with the specific allergen in the absence or presence of IL-12, and assessed by flow cytometry at the single-cell level for their ability to produce IL-4 and/or IFN-gamma after antigen or polyclonal stimulation.

Results: Both IL-12 and the PS-DSP30 oligodeoxynucleotide enabled CRTH2(+) allergen-stimulated T(H)2 cells to produce IFN-gamma. This change in the profile of cytokine production by T(H)2 cells from allergic subjects was related to the upregulation of IL-12 receptor beta2 chain and was associated with the loss of CRTH2.

Conclusions: These data demonstrate that the cytokine production pattern of fully differentiated T(H)2 effectors can be changed to a less polarized profile, thus providing the physiologic basis for new immunotherapeutic strategies in allergic disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology
  • Antigens, Dermatophagoides
  • Cell Line
  • Flow Cytometry
  • Glycoproteins / immunology
  • Humans
  • Hypersensitivity, Immediate / immunology*
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / pharmacology*
  • Interleukin-4 / pharmacology
  • Kinetics
  • Lymphocyte Activation
  • Oligodeoxyribonucleotides / pharmacology*
  • Receptors, Immunologic / analysis*
  • Receptors, Immunologic / metabolism
  • Receptors, Interleukin / biosynthesis
  • Receptors, Interleukin-12
  • Receptors, Prostaglandin*
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*
  • Up-Regulation

Substances

  • Allergens
  • Antigens, Dermatophagoides
  • Glycoproteins
  • IL12RB2 protein, human
  • Oligodeoxyribonucleotides
  • Receptors, Immunologic
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • Receptors, Prostaglandin
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma
  • prostaglandin D2 receptor