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Cord blood CD4CD25 regulatory T cells fail to inhibit cord blood NK cell functions due to insufficient production and expression of TGF-beta1
Authors:Liqing Xu  Shigeki Tanaka  Motoki Bonno  Masaru Ido  Masatoshi Kawai  Hatsumi Yamamoto  Yoshihiro Komada
Affiliation:1. Clinical Research Institute, Mie Chuo Medical Center, National Hospital Organization, Tsu, Mie, Japan;2. Department of Neonatal Science, Institute of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan;3. Shanghai Children’s Medical Center, Shanghai, China;4. Department of Psychology and Social Welfare, School of Letters, Mukogawa Women’s University, Nishinomiya, Hyogo, Japan;5. Department of Pediatrics, Institute of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan
Abstract:Although CD4+CD25+ Treg (Treg) cells are known to modulate NK cell functions, the modulation mechanism of these cells in cord blood has not been fully clarified. The purpose of this study was to clarify the mechanism whereby cord blood Treg cells modulate cord NK cells. By performing various cultures of purified NK cells with or without autologous Treg cells, diminished inhibitory effects of cord Treg cells towards cord NK cell functions, including activation, cytokine production, and cytotoxicity, were observed. We also observed lower secretion of sTGF-beta1 and lower expression of mTGF-beta1 by cord Treg cells than by adult Treg cells. These data revealed the capability of adult Treg cells to suppress rhIL-2-stimulated NK cell function by TGF-beta1, both membrane-bound and soluble types. The reduced inhibitory capabilities of cord Treg cells compared with adult Treg cells is thought to be due to insufficient expression of TGF-beta1.
Keywords:Treg cell, CD4+CD25+ regulatory T cell   NK cell, natural killer cell   PBMCs, peripheral blood mononuclear cells   CBMCs, cord blood mononuclear cells   MLC, mixed lymphocyte culture   FOXP3, forkhead box P3   rhIL-2, recombinant human IL-2   rhTGF-beta1, recombinant human transforming growth factor beta1   mTGF-beta1, membrane-bound transforming growth factor-beta1   sTGF-beta1, soluble transforming growth factor-beta1
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