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KMID : 0578320160390060468
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Molecules and Cells
2016 Volume.39 No. 6 p.468 ~ p.476
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PLZF+ Innate T Cells Support the TGF-β-Dependent Generation of Activated/Memory-Like Regulatory T Cells
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Kang Byung-Hyun
Park Hyo-Jin
Park Hi-Jung
Lee Jae-II
Park Seong-Hoe
Jung Kyeong-Cheon
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Abstract
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PLZF-expressing invariant natural killer T cells and CD4 T cells are unique subsets of innate T cells. Both are selected via thymocyte-thymocyte interaction, and they contribute to the generation of activated/memory-like CD4 and CD8 T cells in the thymus via the production of IL-4. Here, we investigated whether PLZF+ innate T cells also affect the development and function of Foxp3+ regulatory CD4 T cells. Flow cytometry analysis of the thymus and spleen from both CIITA transgenic C57BL/6 and wild-type BALB/c mice, which have abundant PLZF+ CD4 T cells and invariant natural killer T cells, respectively, revealed that Foxp3+ T cells in these mice exhibited a CD103+ activated/memory-like phenotype. The frequency of CD103+ regulatory T cells was considerably decreased in PLZF+ cell-deficient CIITATgPlzflu/lu and BALB/c.CD1d?/? mice as well as in an IL-4-deficient background, such as in CIITATgIL-4?/? and BALB/c.lL-4?/? mice, indicating that the acquisition of an activated/memory-like phenotype was dependent on PLZF+ innate T cells and IL-4. Using fetal thymic organ culture, we further demonstrated that IL-4 in concert with TGF-β enhanced the acquisition of the activated/memory-like phenotype of regulatory T cells. In functional aspects, the activated/memory-like phenotype of Treg cells was directly related to their suppressive function; regulatory T cells of CIITATgPIV?/? mice more efficiently suppressed ovalbumin-induced allergic airway inflammation compared with their counterparts from wild-type mice. All of these findings suggest that PLZF+ innate T cells also augmented the generation of activated/memory-like regulation via IL-4 production.
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KEYWORD
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IL-4, PLZF, regulatory T lymphocyte
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