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


OBJECTIVE
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.


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.
Aguilar-Pimentel
Juan A
JA
Department of Dermatology and Allergy, Biederstein Technische Universität München, Munich, Germany.
Alessandrini
Francesca
F
Huster
Katharina M
KM
Jakob
Thilo
T
Schulz
Holger
H
Behrendt
Heidrun
H
Ring
Johannes
J
de Angelis
Martin Hrabé
MH
Busch
Dirk H
DH
Mempel
Martin
M
Ollert
Markus
M
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000276:immunology; D000485:Allergens / Q000276:immunology; D000818:Animals; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000378:metabolism*; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000485:Allergens; C110366:OVA-8; D010446:Peptide Fragments; C486171:Tap1 protein, mouse; D007073:Immunoglobulin E; D010047:Ovalbumin