Conversion of Th2 memory cells into Foxp3+ regulatory T cells suppressing Th2-mediated allergic asthma.
Genetic and epigenetic programming of T helper (Th) cell subsets during their polarization from naive Th cells establishes long-lived memory Th cells that stably maintain their lineage signatures. However, whether memory Th cells can be redifferentiated into another Th lineage is unclear. In this study, we show that Ag-specific memory Th cells were redifferentiated into Foxp3(+) T cells by TGF-beta when stimulated in the presence of all-trans retinoic acid and rapamycin. The "converted" Foxp3(+) T cells that were derived from Th2 memory cells down-regulated GATA-3 and IRF4 and produced little IL-4, IL-5, and IL-13. Instead, the converted Foxp3(+) T cells suppressed the proliferation and cytokine production of Th2 memory cells. More importantly, the converted Foxp3(+) T cells efficiently accumulated in the airways and significantly suppressed Th2 memory cell-mediated airway hyperreactivity, eosinophilia, and allergen-specific IgE production. Our findings reveal the plasticity of Th2 memory cells and provide a strategy for adoptive immunotherapy for the treatment of allergic diseases.
Kim
Byung-Seok
BS
Laboratory of Immunology, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
Kim
Il-Kyu
IK
Park
Young-Jun
YJ
Kim
Yun-Sun
YS
Kim
Yeon-Jeong
YJ
Chang
Woo-Sung
WS
Lee
Yoon-Sook
YS
Kweon
Mi-Na
MN
Chung
Yeonseok
Y
Kang
Chang-Yuil
CY
D000818:Animals; D001249:Asthma / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000150:complications / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D000939:Epitopes / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology*; D050990:GATA3 Transcription Factor / Q000378:metabolism; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology*; D007249:Inflammation / Q000150:complications / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D020123:Sirolimus / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology
D016207:Cytokines; D000939:Epitopes; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D016212:Transforming Growth Factor beta; D014212:Tretinoin; D020123:Sirolimus