Stimulated human lamina propria T cells manifest enhanced Fas-mediated apoptosis

被引:113
作者
Boirivant, M
Pica, R
DeMaria, R
Testi, R
Pallone, F
Strober, W
机构
[1] UNIV ROMA LA SAPIENZA,GI UNIV,ROME,ITALY
[2] UNIV ROMA TOR VERGATA,DEPT EXPT MED & BIOCHEM SCI,ROME,ITALY
[3] UNIV REGGIO CALABRIA,DEPT EXPT MED,CATANZARO,ITALY
[4] NIAID,NIH,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD
关键词
apoptosis; T lymphocytes; human intestinal lamina propria; regional immunity;
D O I
10.1172/JCI119082
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Lamina propria (LP)T cells respond poorly to a proliferative stimulus delivered via TCR/CD3 pathway, but retain considerable ability to respond to a stimulus delivered via CD2 costimulatory or accessory pathway. in the present study, we showed first that unstimulated LP T cells, as compared to unstimulated peripheral blood (PB)T cells, exhibit an increased level of apoptosis which is further increased following CD2 pathway stimulation, but not following via TCR/CD3 pathway stimulation. We next showed that IL-2 had a sparing effect on apoptosis of unstimulated LP T cells in that IL-2 decreased and anti-IL-2 increased apoptosis of these cells; in contrast, IL-2 had no effect on apoptosis of CD2-pathway stimulated eels. Finally, we showed that increased apoptosis of LP T cells induced by CD2-pathway stimulation is inhibited when Fas antigen is blocked by a nonstimulatory anti-Fas antibody. These studies suggest that LP T cells are characterized by increased susceptibility to Fas-mediated apoptosis most due to a downstream change in the Fas signaling pathway. Given that IFN-gamma secretion is significantly increased in LP T cells in which apoptosis is inhibited, this feature of LP T cells may represent a mechanism of regulating detrimental immune responses in the mucosal environment.
引用
收藏
页码:2616 / 2622
页数:7
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