Survival of Single Positive Thymocytes Depends upon Developmental Control of RIPK1 Kinase Signaling by the IKK Complex Independent of NF-κB

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食管癌细胞膜提取物体外诱导胚胎胸腺细胞抗癌效应的研究

本文探讨增强胚胎胸腺细胞抗肿瘤效应的方法。采用食管癌细胞膜抗原体外诱导培养的胚胎胸腺细胞 ;用3 H TdR掺入法检测其对食管癌细胞的细胞毒效应 ;用SP 免疫组化法检测其经诱导后细胞表面抗原的变化。结果经食管癌细胞膜抗原诱导 3～ 9d的胚胎胸腺细胞对食管癌细胞的杀伤率明显大于未经诱导的胚胎胸腺细胞 ;胚胎胸腺细胞经诱导后CD4 + /CD8+ 细胞无明显变化 ,但诱导后出现少量CD5 6细胞。食管癌细胞膜抗原体外诱导胚胎胸腺细胞可增强其对食管癌细胞的细胞毒作用     

In vitro evidence for participation of DEC-205 expressed by thymic cortical epithelial cells in clearance of apoptotic thymocytes

Binding of apoptotic cells was compared after incubation of thymocytes with two clones of murine thymic stromal cells to which CD4(+)/CD8(+) thymocytes attach. With the BA/10, but not the BA/2, clone, thymocytes with apoptotic morphology were bound irreversibly. These tightly bound thymocytes were further identified as apoptotic in terms of active caspase-3 and DNA fragmentation assayed in situ. FACS analysis indicated that the apoptotic thymocytes are at an early double-positive stage and results with mice mutant for the Fas gene showed that the Fas-Fas ligand system is not involved. Comparison of BA/10 and BA/2 cells showed that the former, but not the latter, can be induced to express CDR-1 antigen which is characteristic of cortical epithelial thymic stroma and constitutively express DEC-205, a surface protein common to cortical thymic epithelium and dendritic cells. Antibody NLDC-145 that is specific for the DEC-205 protein strongly reduced the number of stromal cells with bound apoptotic thymocytes. Preincubation of thymocytes in dexamethasone dramatically increased the number of bound apoptotic cells, indicating that the thymic cortical epithelial cells can participate in clearance of apoptotic thymocytes through involvement of DEC-205.     

FT-2 antigen for distinguishing lymphocyte subpopulations in the developing thymus

The surface phenotypes of lymphoid cells in the developing embryonic thymus were characterized by using monoclonal antibodies. FT-2 antigen thus defined was predominantly expressed on thymocytes in the earlier embryonic stages in all the inbred mouse strains tested. The immunofluorescence and immunoperoxidase tests indicated that, like FT-1 antigen, the proportion of FT-2+ fetal thymocytes rapidly decreased with increase in gestation time, and these cells disappeared by day 19 of gestation. The treatment of fetal thymocytes with anti-FT-1 plus complement eliminated not only FT-1+, but also FT-2+ cells, whereas the treatment with anti-FT-2 failed to eliminate approximately 40% of FT-1+ cells, suggesting that embryonic thymocytes can be provisionally divided into at least three subpopulations, FT-1+2+, FT-1+2- and FT-1-2-.     

实验性糖尿病诱导大鼠胸腺细胞凋亡的电镜观察

目的：探讨糖尿病诱导大鼠胸腺细胞凋亡的形态学变化,从而了解其引起胸腺萎缩的可能机制。方法：采用四氧嘧啶诱导复制的大鼠实验性糖尿病动物模型,在电镜下观察了糖尿病大鼠胸腺细胞凋亡的形态学变化。结果：在糖尿病大鼠胸腺皮质中发现了大量凋亡的胸腺细胞,主要表现为细胞皱缩变小,表面形成许多皱突,似发泡状,细胞质浓缩,电子密度增强,线粒体肿胀,嵴减少与紊乱,空泡化细胞核染色质固缩边聚,核变成花瓣状,黑环状与黑洞状,核与细胞发生裂解形成凋亡小体,被巨噬细胞和上皮细胞吞噬清除。此外,在凋亡细胞与小体的周围还聚着许多浆细胞,结论：实验性糖尿病可诱导大鼠脑腺细胞发生大量凋亡,这可能是导致胸腺细胞大量减少及胸腺萎缩的主要机制之一。     

Thymocyte maturation is regulated by the activity of the helix-loop-helix protein, E47

The E2A proteins, E12 and E47, are required for progression through multiple developmental pathways, including early B and T lymphopoiesis. Here, we provide in vitro and in vivo evidence demonstrating that E47 activity regulates double-positive thymocyte maturation. In the absence of E47 activity, positive selection of both major histocompatibility complex (MHC) class I- and class II-restricted T cell receptors (TCRs) is perturbed. Additionally, development of CD8 lineage T cells in an MHC class I-restricted TCR transgenic background is sensitive to the dosage of E47. Mice deficient for E47 display an increase in production of mature CD4 and CD8 lineage T cells. Furthermore, ectopic expression of an E2A inhibitor helix-loop-helix protein, Id3, promotes the in vitro differentiation of an immature T cell line. These results demonstrate that E2A functions as a regulator of thymocyte positive selection.