CELLULAR AND PEPTIDE REQUIREMENTS FOR INVITRO CLONAL DELETION OF IMMATURE THYMOCYTES
CELLULAR AND PEPTIDE REQUIREMENTS FOR INVITRO CLONAL DELETION OF IMMATURE THYMOCYTES
复制标题
DOI：
10.1073/pnas.89.19.9000
复制
发表时间：
1992-10-01
影响因子：
11.1
通讯作者：
LOH, DY
中科院分区：
文献类型：
--
作者：
IWABUCHI, K;NAKAYAMA, K;LOH, DY
当鸡卵清蛋白-（323-339）肽在体内给药时，来自DO 10 T细胞受体转基因小鼠的胸腺细胞经历凋亡或程序性细胞死亡。使用DO 10小鼠胸腺细胞，我们现在已经开发了一个简单的体外模型系统，概括了在体内克隆删除过程。当转基因胸腺细胞与成纤维细胞、B细胞或胸腺滋养细胞系（均携带I-A（d））在鸡卵清蛋白-（323-339）存在下共培养时，在8-20小时内观察到转基因TCR+ CD 4 + CD 8+胸腺细胞的缺失。因此，胸腺细胞克隆缺失完全取决于胸腺细胞易受凋亡发生的阶段，而不是肽抗原呈递细胞的性质。此外，胸腺保育细胞系TNC-R3.1可导致缺失，强烈表明某些胸腺上皮/基质成分可能能够参与负选择。在所有检查的情况下，在肽浓度下几乎不能诱导缺失。
Thymocytes from DO10 T-cell-receptor transgenic mice undergo apoptosis, or programmed cell death, when chicken ovalbumin-(323-339) peptide is administered in vivo. Using DO10 mice thymocytes, we have now developed a simple in vitro model system that recapitulates the in vivo clonal-deletion process. When transgenic thymocytes were cocultured with fibroblasts, B cells, or thymic nurse cell lines (all bearing I-A(d)) in the presence of chicken ovalbumin-(323-339), deletion of the transgenic TCR+CD4+CD8+ thymocytes was seen within 8-20 hr. Thymocytes designed to bear I-A(d) on their surface could mediate the deletion themselves. Thus, thymocyte clonal deletion entirely depends on the stage at which the thymocytes are vulnerable to the onset of apoptosis, rather than on the nature of the peptide antigen-presenting cells. Furthermore, thymic nurse cell line TNC-R3.1 could cause deletion, strongly suggesting that some thymic epithelial/stromal components are potentially capable of participating in negative selection. In all cases examined, little deletion could be induced at a peptide concentration