Summary: | 碩士 === 長庚大學 === 基礎醫學研究所 === 93 === Regulatory T cells (Treg cells) are subsets of CD4+ T cells and have the suppressive capacity to down-regulate the activation and expansion of self-reactive lymphocytes. They are divided into two major subtypes: natural Treg cells and adaptive Treg cells based on the ontogeny and mode of action. In this study, I explored the suppressive mechanism of Treg cells by an in vitro readout system using a Hemagglutinin (HA)-specific transgenic TCR mice model. The results suggest that CD4+CD25+ Treg cells from 6.5 mice, consistent with those from wild-type B10D2 mice, have suppressive capacity to effectively inhibit proliferation and IFN-gamma production of T responder cells which were activated by HA peptide or anti-CD3 mAbs in the presence of T cell-depleted splenocytes served as antigen-presenting cells. However, in the presence of LPS-DCs, natural Treg cells, from 6.5 and B10D2 mice, lose the inhibitory ability to proliferation and IFN-gamma production of T responder cells. This breakage of suppression has been documented that may be due to IL-6 produced by LPS-DCs and some unidentified molecules. Although addition of exogenous IL-2 does overcome suppression of proliferation, but production of IFN-gamma is still hampered. Analysis of phosphorylated STAT1 of responder cells has indicated that loss of IFN-gamma production after stimulation may be related to phosphorylated STAT1 down-regulation in the presence of natural Treg cells. This study provides insight into mechanism of Treg function.
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