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  • 标题:A transgenic mouse model to analyze CD8+ effector T cell differentiation in vivo
  • 本地全文:下载
  • 作者:N. Manjunath ; P. Shankar ; B. Stockton
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:1999
  • 卷号:96
  • 期号:24
  • 页码:13932-13937
  • DOI:10.1073/pnas.96.24.13932
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Antigen-specific effector T cells are prerequisite to immune protection, but because of the lack of effector cell-specific markers, their generation and differentiation has been difficult to study. We report that effector cells are highly enriched in a T cell subset that can be specifically identified in transgenic (T-GFP) mice expressing green fluorescent protein (GFP) under control of the murine CD4 promoter and proximal enhancer. Consistent with previous studies of these transcriptional control elements, GFP was strongly and specifically expressed in nearly all resting and short-term activated CD4+ and CD8+ T cells. However, when T-GFP mice were challenged with vaccinia virus, allogeneic tumor cells, or staphylococcal enterotoxin A, the cytotoxic and IFN-{gamma}-producing T cells lost GFP expression. Upon T cell receptor (TCR) ligation by CD3, sorted GFP+ cells fluxed calcium and proliferated vigorously. In contrast, GFP- effector cells showed a diminished calcium flux and did not proliferate. Instead, they underwent apoptosis unless supplied with exogenous IL-2. By reverse transcription-PCR analysis, the GFP- cells up-regulated the pro-apoptotic molecule, Fas-L, and down-regulated gene expression of the proximal TCR signaling molecule, CD3{zeta
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