RGD Reference Report - Allergen-specific CTL require perforin expression to suppress allergic airway inflammation. - Rat Genome Database

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Allergen-specific CTL require perforin expression to suppress allergic airway inflammation.

Authors: Enomoto, N  Hyde, E  Ma, JZ  Yang, J  Forbes-Blom, E  Delahunt, B  Le Gros, G  Ronchese, F 
Citation: Enomoto N, etal., J Immunol. 2012 Feb 15;188(4):1734-41. Epub 2012 Jan 16.
RGD ID: 6482815
Pubmed: PMID:22250087   (View Abstract at PubMed)
DOI: DOI:10.4049/jimmunol.1102699   (Journal Full-text)

Allergen-specific CTL have a protective effect on allergic airway inflammation, a function thought to be mediated by cytokines, especially IFN-gamma. However, the contribution of cytotoxic function to this protective effect has not been investigated. We examined the contribution of cytotoxic function to the therapeutic effect of allergen-specific CTL in allergic airway inflammation. We used a murine model of allergic airway inflammation in which mice were sensitized to OVA and then challenged with the same Ag via the intranasal route. CTL were elicited in these mice by immunization with dendritic cells (DC) or by adoptive transfer of in vitro-activated CD8(+) T cells. Hallmark features of allergic asthma, such as infiltration of eosinophils in the bronchoalveolar lavage fluid and mucus production, were assessed. Suppression of allergic airway inflammation by allergen-specific CTL was critically dependent on the expression of perforin, a key component of the cytotoxic machinery. Both perforin-sufficient and perforin-deficient allergen-specific CTL were recovered from the lungs of allergen-sensitized mice and upregulated CD69 expression and secreted the cytokines IFN-gamma and TNF-alpha upon intranasal allergen challenge. However, only perforin-sufficient CTL inhibited eosinophil infiltration in the airway, mucus production, and cytokine accumulation in the bronchoalveolar lavage fluid. Treatment with allergen-specific CTL, but not their perforin-deficient counterparts, was also associated with a decrease in the number of DC in the mediastinal lymph node. Our data suggest that the cytotoxic function of allergen-specific CD8(+) T cells is critical to their ability to moderate allergic airway inflammation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
asthma  ISOPrf1 (Mus musculus)6482815; 6482815 RGD 
asthma  IMP 6482815 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Prf1  (perforin 1)

Genes (Mus musculus)
Prf1  (perforin 1 (pore forming protein))

Genes (Homo sapiens)
PRF1  (perforin 1)


Additional Information