1. Conversion of Th2 memory cells into [Foxp3.sup.+] regulatory T cells suppressing Th2-mediated allergic asthma
- Author
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Kim, Byung-Seok, Kim, Il-Kyu, Park, Young-Jun, Kim, Yun-Sun, Kim, Yeon-Jeong, Chang, Woo-Sung, Lee, Yoon-Sook, Kweon, Mi-Na, Chung, Yeonseok, and Kang, Chang-Yuil
- Subjects
Immunoglobulin E -- Properties ,T cells -- Properties ,Tretinoin -- Dosage and administration ,Asthma -- Drug therapy ,Immunological tolerance -- Research ,Adaptation (Physiology) -- Research ,Immunotherapy -- Methods ,Rapamycin -- Dosage and administration ,Science and technology - Abstract
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.sup.+] T cells by TGF-[beta] when stimulated in the presence of all-trans retinoic acid and rapamycin. The 'converted' [Foxp3.sup.+] 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.sup.+] T cells suppressed the proliferation and cytokine production of Th2 memory cells. More importantly, the converted [Foxp3.sup.+] 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. all-trans retinoic acid | immune tolerance | immunotherapy | plasticity | rapamycin doi/10.1073/pnas.0911756107
- Published
- 2010