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


CONCLUSIONS
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.
Karwot
Roman
R
Laboratory of Cellular and Molecular Immunology of the Lung, I. Medical Clinic, University of Mainz, Mainz, Germany.
Maxeiner
Joachim H
JH
Schmitt
Steffen
S
Scholtes
Petra
P
Hausding
Michael
M
Lehr
Hans A
HA
Glimcher
Laurie H
LH
Finotto
Susetta
S
D019264:Adoptive Transfer; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005260:Female; D006131:Growth Inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics; D020381:Interleukin-17 / Q000096:biosynthesis; D053646:Interleukin-2 Receptor beta Subunit / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D050778:NFATC Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D015854:Up-Regulation / Q000276:immunology
D006131:Growth Inhibitors; D020381:Interleukin-17; D053646:Interleukin-2 Receptor beta Subunit; D050778:NFATC Transcription Factors; C494007:Nfatc2 protein, mouse; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain; D007371:Interferon-gamma