Abstract:
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.
journal_name
Am J Respir Crit Care Medauthors
Aguilar-Pimentel JA,Alessandrini F,Huster KM,Jakob T,Schulz H,Behrendt H,Ring J,de Angelis MH,Busch DH,Mempel M,Ollert Mdoi
10.1164/rccm.200902-0190OCsubject
Has Abstractpub_date
2010-01-01 00:00:00pages
7-16issue
1eissn
1073-449Xissn
1535-4970pii
200902-0190OCjournal_volume
181pub_type
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