Román Eulogia, Shino Hanabuchi, Qin F Xiao-Feng, Liu Yong Jun
Department of Immunology, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
J Immunol. 2010 Oct 1;185(7):3819-23. doi: 10.4049/jimmunol.0900665. Epub 2010 Aug 27.
Recognition of self-peptide-MHC complexes by high-affinity TCRs and CD28 signaling are critical for the development of forkhead-winged helix box transcription factor 3(+) regulatory T cells (Tregs) in thymus. However, the type of APCs that are responsible for selecting Tregs has remained unclear. To dissect the role of hematopoietic-derived APCs (HCs) and thymic epithelial cells (TECs) in Treg selection, we constructed bone marrow chimeras with disrupted CD28/B7 signaling in the HC or TEC compartment and analyzed the generation of Tregs in the thymus. We found that both HCs and TECs were independently able to fully reconstitute the Treg population in the thymus of bone marrow chimeras. In addition, Treg selection requires the TCR signal and CD28 costimulation presented in cis on the same APC type in vivo. This study demonstrates a new role, to our knowledge, for HCs in the development of Tregs in thymus.
高亲和力T细胞受体对自身肽 - 主要组织相容性复合体的识别以及CD28信号传导对于胸腺中叉头翼状螺旋盒转录因子3（+）调节性T细胞（Tregs）的发育至关重要。然而，负责选择Tregs的抗原呈递细胞（APC）类型仍不清楚。为了剖析造血来源的APC（HCs）和胸腺上皮细胞（TECs）在Treg选择中的作用，我们构建了在HC或TEC区室中具有破坏的CD28 / B7信号传导的骨髓嵌合体，并分析了胸腺中Tregs的产生。我们发现，HCs和TECs都能够独立地完全重建骨髓嵌合体胸腺中的Treg群体。此外，Treg选择需要体内同一APC类型上顺式呈现的TCR信号和CD28共刺激。据我们所知，这项研究证明了HCs在胸腺中Tregs发育中的新作用。
