Increased immunosuppressive function of CD4(+)CD25(+)Foxp3(+)GITR+ T regulatory cells from NFATc2((-/-)) mice controls allergen-induced experimental asthma.
The expansion of effector T cells is tightly controlled by transcription factors like nuclear factor of activated T cells (NFAT) family members that mediate early intracellular responses to T cell receptor-mediated signals. In this study we show that, after allergen challenge, NFATc2((-/-)) mice had augmented number of functionally intact CD4(+)CD25(++)GITR(++) T regulatory (T regs) cells in the lung. Anti-GITR antibody treatment inhibited T regulatory cell function and enhanced the number of activated lung CD4(+) T cells associated with increased IL-2 and pSTAT-5 in the airways of NFATc2((-/-)) mice in experimental allergic asthma. This agonistic treatment led to increased inflammation in the lung of NFATc2((-/-)) treated mice. These data indicate that NFATc2((-/-)) mice have increased number of CD4(+)CD25(+)Foxp3(+) T regulatory cells with induced immunosuppressive function that control allergen-induced experimental asthma.
Laboratory of Cellular and Molecular Immunology of the Lung, Institute of Molecular Medicine, University of Mainz, 55131 Mainz, Germany.
Roman
R
Karwot
Caroline
C
Übel
Tobias
T
Bopp
Edgar
E
Schmitt
Susetta
S
Finotto
D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000276:immunology*; D015704:CD4 Antigens / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D053450:Glucocorticoid-Induced TNFR-Related Protein / Q000276:immunology / Q000378:metabolism; D007165:Immunosuppression Therapy; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D050778:NFATC Transcription Factors / Q000172:deficiency* / Q000235:genetics; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000485:Allergens; D015704:CD4 Antigens; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053450:Glucocorticoid-Induced TNFR-Related Protein; D053645:Interleukin-2 Receptor alpha Subunit; D050778:NFATC Transcription Factors; C106544:Tnfrsf18 protein, mouse