Activation events during thymic selection.
Activation events during thymic selection.
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DOI：
10.1084/jem.175.3.731
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发表时间：
1992-03-01
期刊：
影响因子：
--
通讯作者：
Schwartz RH
中科院分区：
文献类型：
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作者：
Bendelac A;Matzinger P;Seder RA;Paul WE;Schwartz RH
在小鼠胸腺的分化过程中，CD4+8-细胞经历了成熟的外周CD4+淋巴细胞正常活化时观察到的一系列变化。CD69是一种早期激活标志物，在T细胞受体（TCR）低/中双阳性阶段的少数细胞中首次观察到表达，在热稳定抗原（HSA）高TCRhi双阳性、HSAhi TCRmed CD4+8lo和HSAhi TCRhi CD4+8-细胞中表达最多（50-90%），并在成熟的HSAlo CD4+8-阶段下调。相反，CD44，一种晚期激活标记物，在HSAlo阶段被选择性表达。CD4+8-胸腺细胞在受到刺激后产生的淋巴因子也具有特征性，从HSAhi期主要的白介素2 （IL-2）增加到HSAlo期的IL-2和大量的IL-4、IL-5、IL-10和干扰素γ (ifn - γ)。1 / 30的HSAlo CD4+8-成年胸腺细胞通过TCR刺激分泌IL-4。这个频率是IL-2产生细胞频率的25%，大约是外周（主要是静止的）CD4+ T细胞频率的100倍。在器官培养中产生CD4+8-胸腺细胞后，随着时间的推移，CD4+8-胸腺细胞失去分泌IL-4、IL-5和ifn - γ的能力，但不会分泌IL-2。同样，通过新生儿胸腺和脾脏CD4+细胞的直接比较，或者通过成人胸腺内标记的CD4+8-细胞迁移到脾脏后的命运判断，IL-4的频率（而不是IL-2）在迁移到外周后逐渐降低。这一序列表明，胸腺选择是激活过程的结果，而不是双阳性阶段对死亡的简单拯救，并表明胸腺内激活后引起的功能变化，尽管是短暂的，但在输出到外周后仍然明显。
During their differentiation in the mouse thymus, CD4+8- cells undergo several of the sequential changes observed upon normal activation of mature, peripheral CD4+ lymphocytes. Expression of CD69, an early activation marker, is first observed on a minority of cells at the T cell receptor (TCR)lo/med double-positive stage, is maximal (50-90%) on heat-stable antigen (HSA)hi TCRhi double-positive, HSAhi TCRmed CD4+8lo, and HSAhi TCRhi CD4+8- cells, and is downmodulated at the mature HSAlo CD4+8- stage. In contrast, CD44, a late activation marker, is selectively expressed at the HSAlo stage. The set of lymphokines that CD4+8- thymocytes can produce upon stimulation also characteristically expands from mainly interleukin 2 (IL-2) at the HSAhi stage, to IL-2 and very large amounts of IL-4, IL-5, IL-10, and interferon gamma (IFN-gamma) at the HSAlo stage. 1 in 30 HSAlo CD4+8- adult thymocytes secrete IL-4 upon stimulation through their TCR. This frequency is 25% of the frequency of IL-2 producers, about 100-fold above that of peripheral (mainly resting) CD4+ T cells. With time after their generation in organ culture, CD4+8- thymocytes lose their capacity to secrete IL-4, IL-5, and IFN-gamma, but not IL-2. Similarly, the frequency of IL-4, but not of IL-2, producers progressively decreases after emigration to the periphery as judged by direct comparison between thymic and splenic CD4+ cells in newborns, or by following the fate of intrathymically labeled CD4+8- cells in adults after their migration to the spleen. This sequence suggests that thymic selection results from an activation process rather than a simple rescue from death at the double-positive stage, and shows that the functional changes induced after intrathymic activation, although transient, are still evident after export to the periphery.