Positive selection is an early event in thymocyte differentiation: high TCR expression by cycling immature thymocytes precedes final maturation by several days.
Positive selection is an early event in thymocyte differentiation: high TCR expression by cycling immature thymocytes precedes final maturation by several days.
复制标题
正选择是胸腺细胞分化的早期事件：循环未成熟胸腺细胞的高 TCR 表达先于最终成熟几天。
DOI：
10.1093/intimm/2.7.629
复制
发表时间：
1990
影响因子：
4.4
通讯作者：
C. Pénit
中科院分区：
文献类型：
--
作者：
C. Pénit
用流式细胞术分析了胸腺细胞周期和周期后T细胞抗原受体的表达。给正常小鼠注射5-溴-2‘-脱氧尿苷(BrdUrd)，这是一种可用单抗检测到的胸苷类似物。用几种Vβ基因产物和整个αβ受体的抗体对胸腺细胞进行表面染色，并在酶促产生单链DNA后检测细胞核中的BrdUrd。在周期中发现有10%的胸腺细胞表达高水平的α-βTCR：这些细胞是未成熟的，如CD4+8+表型和高HSA表达所示。分裂后，大多数高α-β高BrdUrd+细胞进入静息状态，其数量在3天内保持不变，此后分两步减少。这种有丝分裂后的进化不能通过注射抗有丝分裂药物来改变。在第4天后，大多数研究亚群获得了单一的阳性表型。冰冻切片上BrdUrd+Vβ8.2高表达细胞定位于早期皮质区和3d后髓质。分析了不同品系小鼠胸腺细胞周期和周期后Vβ6的表达，发现胸腺细胞周期早期高表达仅限于mis 1b品系。这些结果表明，未成熟胸腺细胞周期中α-βTCR的高表达对应于正选择，因此这必须被认为是胸腺内分化的早期事件。
T cell antigen receptor expression by cycling and post-cycling thymocytes has been analysed by flow cytometry. Normal mice were pulsed with 5-bromo-2'-deoxyuridine (BrdUrd), a thymidine analogue detectable with a monoclonal antibody. Thymocytes were surface-stained with antibodies against several V beta gene products and against whole alpha beta receptors and detection of BrdUrd in the nuclei was performed after enzymatic generation of single-stranded DNA. A significant (10%) percentage of thymocytes expressing high levels of alpha beta TCR were found in the cycle: these cells were immature, as shown by the CD4+8+ phenotype and by high HSA expression. After division, most alpha beta high BrdUrd+ cells entered a resting state and their number remained constant for 3 days, decreasing in two steps thereafter. This post-mitotic evolution was not modified by injection of an anti-mitotic drug. After day 4, a majority of the studied subset acquired a single positive phenotype. Location of BrdUrd+ V beta 8.2 high cells studied on frozen sections was found cortical at early times and medullary after day 3. V beta 6 expression by cycling and post-cycling thymocytes was analysed in various mouse strains, and early high expression by cycling thymocytes was found to be restricted to MIs 1b strains. These results suggest that high alpha beta TCR expression by cycling immature thymocytes corresponds to positive selection, which must therefore be considered as an early event in intrathymic differentiation.