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http://dx.doi.org/10.14348/molcells.2016.0004

PLZF+ Innate T Cells Support the TGF-β-Dependent Generation of Activated/Memory-Like Regulatory T Cells  

Kang, Byung Hyun (Postgraduate Course of Translational Medicine, Seoul National University College of Medicine)
Park, Hyo Jin (Department of Pathology, Seoul National University College of Medicine)
Park, Hi Jung (Postgraduate Course of Translational Medicine, Seoul National University College of Medicine)
Lee, Jae-Il (Postgraduate Course of Translational Medicine, Seoul National University College of Medicine)
Park, Seong Hoe (Postgraduate Course of Translational Medicine, Seoul National University College of Medicine)
Jung, Kyeong Cheon (Postgraduate Course of Translational Medicine, Seoul National University College of Medicine)
Publication Information
Molecules and Cells / v.39, no.6, 2016 , pp. 468-476 More about this Journal
Abstract
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/memorylike phenotype. The frequency of $CD103^+$ regulatory T cells was considerably decreased in $PLZF^+$ cell-deficient $CIITA^{Tg}Plzf^{lu/lu}$ and $BALB/c.CD1d^{-/-}$ mice as well as in an IL-4-deficient background, such as in $CIITA^{Tg}IL-4^{-/-}$ and $BALB/c.IL-4^{-/-}$ 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-${\beta}$ 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 $CIITA^{Tg}PIV^{-/-}$ 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.
Keywords
IL-4; PLZF; regulatory T lymphocyte;
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