Specific CD8 T cells in IgE-mediated allergy correlate with allergen dose and allergic phenotype

Am J Respir Crit Care Med. 2010 Jan 1;181(1):7-16. doi: 10.1164/rccm.200902-0190OC. Epub 2009 Oct 8.


Rationale: Studies in humans and rodents have indicated a causative role for CD8(+) T cells in IgE-mediated allergic inflammation, but their function is still controversial.

Objectives: To analyze the role of allergen-specific CD8(+) T cells during the development of allergic airway inflammation in two parallel but diverging outcome models.

Methods: We used H2-Kb SIINFEKL (OVA(257-264)) multimers to analyze induction, natural distribution, and phenotype of allergen-specific CD8(+) T cells in a murine C57BL/6 model of ovalbumin (OVA)-induced allergic airway inflammation using low-dose or high-dose OVA sensitization.

Measurements and main results: The low-dose protocol was characterized by a significant induction of total and OVA-specific IgE, eosinophilic airway inflammation, IL-4 levels in bronchoalveolar lavage fluid. And significant alterations in lung function. The high dose protocol was characterized by a significant reduction of the allergic phenotype. Using OVA(257-264) H2-Kb multimers, we observed lung and airway infiltrating OVA-specific CD8(+) T cells showing an effector/effector-memory phenotype. The high-dose protocol caused significantly higher infiltration of allergen-specific CD8(+) cells to the airways and enhanced their cytotoxicity. Adoptive transfer with CD8(+) T cells from transgenic OT-I mice to TAP1(-/-) or wild-type mice showed their migration to the lungs and TAP1-dependent proliferation after OVA-aerosol exposure. TAP1(-/-) mice defective in CD8(+) T cells showed exacerbated symptoms in the low-dose sensitization model.

Conclusions: Allergen-specific CD8(+) T cells seem to protect from allergic inflammation in the lungs. Their number, which is dependent on the sensitization dose, appears to be a critical predictor for the severity of the allergic phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters / immunology
  • Allergens / immunology
  • Animals
  • Bronchial Provocation Tests
  • Bronchoalveolar Lavage Fluid / immunology
  • CD8-Positive T-Lymphocytes / classification
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Flow Cytometry
  • Hypersensitivity / immunology*
  • Immunoglobulin E / metabolism*
  • Immunologic Memory*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Ovalbumin / immunology
  • Peptide Fragments / immunology


  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters
  • Allergens
  • OVA-8
  • Peptide Fragments
  • Tap1 protein, mouse
  • Immunoglobulin E
  • Ovalbumin