Aguilar L K, Aguilar-Cordova E, Cartwright J, Belmont J W
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, TX 77030.
J Immunol. 1994 Mar 15;152(6):2645-51.
Thymic stromal cells play important roles in thymocyte differentiation and selection. Thymic nurse cells (TNC) are thymic epithelial stromal cells that envelop two to 200 CD4+CD8+ thymocytes (TNC-T). The mechanism by which TNC complexes form and their role in thymocyte development are unknown. TNC have been implicated as specialized microenvironments for proliferation, positive selection, negative selection, and apoptosis. Using TCR-gamma junctional sequence analysis of thymocytes within individual TNC, eight of ten TNC analyzed were polyclonal, and two showed evidence of oligoclonality. TCR-alpha beta expression was not detectable on most TNC-T and SCID mice, which do not express TCRs because of a defect in TCR gene rearrangement, had normal numbers of thymocyte-bearing TNC. Thus, TCR expression is not necessary for TNC formation. Treatment of mice with Abs to CD3 epsilon, which induces apoptosis in immature thymocytes, resulted in an eightfold increase in TNC per thymus with 95.5% apoptotic TNC-T. These results suggest that a function of TNC is the clearance of nonfunctional, nonselected, apoptotic thymocytes.
胸腺基质细胞在胸腺细胞分化和选择中发挥重要作用。胸腺哺育细胞(TNC)是胸腺上皮基质细胞,可包裹2至200个CD4 + CD8 +胸腺细胞(TNC-T)。TNC复合物形成的机制及其在胸腺细胞发育中的作用尚不清楚。TNC被认为是增殖、阳性选择、阴性选择和凋亡的特殊微环境。通过对单个TNC内胸腺细胞的TCR-γ连接序列分析,所分析的10个TNC中有8个是多克隆的,2个显示出寡克隆性的证据。在大多数TNC-T和SCID小鼠(由于TCR基因重排缺陷而不表达TCR)上未检测到TCR-αβ表达,但其带有胸腺细胞的TNC数量正常。因此,TCR表达对于TNC形成并非必需。用抗CD3ε抗体处理小鼠,可诱导未成熟胸腺细胞凋亡,结果导致每个胸腺中TNC增加8倍,其中95.5%的TNC-T发生凋亡。这些结果表明,TNC的一个功能是清除无功能、未被选择的凋亡胸腺细胞。