Protective role of nuclear factor of activated T cells 2 in CD8+ long-lived memory T cells in an allergy model.

Details

Serval ID
serval:BIB_3DB3A28A9B3E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Protective role of nuclear factor of activated T cells 2 in CD8+ long-lived memory T cells in an allergy model.
Journal
Journal of Allergy and Clinical Immunology
Author(s)
Karwot R., Maxeiner J.H., Schmitt S., Scholtes P., Hausding M., Lehr H.A., Glimcher L.H., Finotto S.
ISSN
1097-6825[electronic]
Publication state
Published
Issued date
2008
Volume
121
Number
4
Pages
992-9.e6
Language
english
Abstract
BACKGROUND: The transcriptional regulation of cytokines released and controlled by memory T cells is not well understood. Defective IFN-gamma production in allergic asthma correlates in human beings with the risk of wheezing in childhood. OBJECTIVE: To understand the role of the transcription factor nuclear factor of activated T cells 2 (NFATc2) in memory and effector T cells in the airways in experimental allergic asthma. METHODS: We used murine models of allergic asthma and adoptive cell transfer of fluorescence-activated sorted cells in a disease model. RESULTS: Mice lacking NFATc2 developed an increase in airwayhyperresponsiveness (AHR), remodeling, and serum IgE levelson ovalbumin sensitization. This phenotype was associated withCD81CD1222 T cells deficient in IFN-g production in theairways. The origin of this phenotype in NFATc2(2/2) mice wasrelated to an expanded population of lung CD81CD1221(IL-2Rb chain) CD127hi (IL-7 receptor [R] a chain1) long-livedmemory cells. Adoptive transfer of ovalbumin-specific CD81NFATc2(2/2) T cells enhanced the AHR generated byNFATc2(2/2) CD41 T cells in immunodeficient mice, increasedIL-17, and reduced IFN-g production in the reconstituted mice.Depletion of the memory CD81CD1221IL-7Rhigh T-cellpopulation corrected the defect in IFN-g production by lungNFATc2(2/2) CD81CD1222 cells and abrogated the increasedAHR observed in NFATc2(2/2) CD81 T-cell-reconstituted micewith a severe combined immunodeficiency disorder. CONCLUSION: Taken together, our results suggest that NFATc2 expression in long-lived memory CD8+ T cells controls IL-2 and IFN-gamma production in lung CD8+ T cells, which then limits TH17 and TH2 development in the airways during allergen challenge.
Keywords
Adoptive Transfer, Animals, Bronchial Hyperreactivity, CD8-Positive T-Lymphocytes, Cell Differentiation, Female, Growth Inhibitors, Hypersensitivity, Immunologic Memory, Interferon-gamma, Interleukin-17, Interleukin-2 Receptor beta Subunit, Lung, Male, Mice, Mice, Inbred BALB C, Mice, Knockout, Mice, SCID, NFATC Transcription Factors, Receptors, Interleukin-7, T-Lymphocyte Subsets, Up-Regulation
Pubmed
Web of science
Create date
25/06/2008 10:40
Last modification date
20/08/2019 13:34
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