The roles of Fas/APO-1 (CD95) and TNF in antigen-induced programmed cell death in T cell receptor transgenic mice
The roles of Fas/APO-1 (CD95) and TNF in antigen-induced programmed cell death in T cell receptor transgenic mice
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DOI：
10.1016/s1074-7613(00)80306-4
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发表时间：
1996-07-01
期刊：
影响因子：
32.4
通讯作者：
McDevitt, HO
中科院分区：
文献类型：
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作者：
Sytwu, HK;Liblau, RS;McDevitt, HO
Fas/APO-1（CD 95）和TNF参与胸腺细胞和成熟T细胞抗原特异性AICD的可能性已被研究。使用流感血凝素（HA）特异性TCRtg小鼠的体内抗原刺激来证明，在具有正常（+/+）或缺陷型Fas（lpr/lpr）背景的小鼠中，胸腺细胞和外周CD 4（+）T细胞缺失的动力学是相似的，表明Fas非依赖性途径负责活化T细胞的缺失。注射鼠TNF阻断MAb（TN 3）的TCRtg-+/+或TCRtg-lpr/lpr小鼠在HA刺激后显示胸腺细胞快速凋亡，表明通过Fas和TNF受体的死亡信号对于HA诱导的胸腺细胞缺失不是必需的。TCRtg-lpr/lpr小鼠中的CD 4（+）外周T细胞在注射HA和TN 3后没有发生凋亡，表明TNF介导的凋亡参与抗原刺激后成熟T细胞的缺失。然而，在注射TN 3的TCRtg-/+小鼠中仍然发生凋亡，表明Fas和TNF介导的细胞死亡都可以导致活化的外周T细胞的缺失。
The possible involvement of Fas/APO-1 (CD95) and TNF in antigen-specific AICD of thymocytes and mature T cells has been investigated. Antigenic stimulation in vivo of influenza hemagglutinin (HA)-specific TCRtg mice was used to demonstrate that the kinetics of thymocyte and peripheral CD4(+) T cell deletion are similar in mice with normal (+/+) or defective Fas (lpr/lpr) background, indicating that a Fas-independent pathway(s) is responsible for the deletion of activated T cells. TCRtg-+/+ or TCRtg-lpr/lpr mice injected with murine TNF-blocking MAb (TN3) showed rapid apoptosis of thymocytes after HA stimulation, indicating that death signaling through Fas and TNF receptors is not essential for HA-induced thymocyte deletion. CD4(+) peripheral T cells in TCRtg-lpr/lpr mice did not undergo apoptosis following injection with HA and TN3, indicating that TNF-mediated apoptosis is involved in the deletion of mature T cells after antigenic stimulation. However, apoptosis still occurred in TCRtg-+/+ mice injected with TN3, indicating that both Fas- and TNF-mediated cell death can contribute to the deletion of activated peripheral T cells.