Pezzano M, Samms M, Guyden J C
Department of Biology, The City College of New York, New York, USA.
Ethn Dis. 2001 Winter;11(1):154-6.
Apoptosis of thymocytes associated with thymic nurse cells (TNCs) has been well-documented. TNCs selectively bind and internalize immature alphabeta TCRlo CD4+ CD8+ thymocytes in vitro. A subset of the internalized population matures to the alphabeta TCRhi CD69hi stage of development while the fraction that remains within the cytoplasm dies through the process of apoptosis. Negative selection by thymic cortical epithelial cells has been reported, but little is known about the apoptotic pathway(s) employed to facilitate the death signal. Using the TNC line tsTNC-1 that was reported earlier to maintain the ability to internalize alphabeta TCRlo CD4+ CD8+ cells in vitro, we investigated the role of Fas and TNFalpha in TNC-induced apoptosis. Our initial studies revealed that tsTNC-1 cells express both FasL and TNFalpha apoptosis of triple positive cells was shown to be reduced approximately 50% in co-cultures of tsTNC-1 cells and thymocytes in the presence of either anti-TNFalpha or Fas-Fc. When maximum effective concentrations of both TNFalpha, and Fas-Fc were added to these co-cultures, apoptotic death was further reduced to approximately 68%. These results suggest that both TNFalpha and Fas apoptotic pathways are active during thymocyte selection by TNCs.
胸腺细胞与胸腺哺育细胞（TNCs）相关的凋亡已有充分记录。TNCs在体外能选择性结合并内化未成熟的αβ TCRlo CD4+ CD8+胸腺细胞。内化群体中的一部分会发育成熟至αβ TCRhi CD69hi阶段，而留在细胞质内的部分则通过凋亡过程死亡。胸腺皮质上皮细胞进行的阴性选择已有报道，但对于促使死亡信号产生的凋亡途径知之甚少。利用先前报道的能在体外保持内化αβ TCRlo CD4+ CD8+细胞能力的TNC系tsTNC-1，我们研究了Fas和TNFα在TNC诱导的凋亡中的作用。我们的初步研究表明，tsTNC-1细胞同时表达FasL和TNFα，在存在抗TNFα或Fas-Fc的情况下，tsTNC-1细胞与胸腺细胞的共培养中，三阳性细胞的凋亡显示减少了约50%。当将TNFα和Fas-Fc的最大有效浓度添加到这些共培养物中时，凋亡死亡进一步减少至约68%。这些结果表明，在TNCs对胸腺细胞的选择过程中，TNFα和Fas凋亡途径均处于活跃状态。
