信号转导和转录激活因子5（STAT5）激活对CD4+和CD8+ T细胞稳态的不同影响：CD4+CD25+调节性T细胞与CD8+记忆性T细胞的发育

Distinct effects of STAT5 activation on CD4+ and CD8+ T cell homeostasis: development of CD4+CD25+ regulatory T cells versus CD8+ memory T cells.

作者信息

Burchill Matthew A, Goetz Christine A, Prlic Martin, O'Neil Jennifer J, Harmon Ian R, Bensinger Steven J, Turka Laurence A, Brennan Paul, Jameson Stephen C, Farrar Michael A

机构信息

Center for Immunology, Cancer Center, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.

出版信息

J Immunol. 2003 Dec 1;171(11):5853-64. doi: 10.4049/jimmunol.171.11.5853.

DOI:10.4049/jimmunol.171.11.5853

PMID:14634095

Abstract

Using transgenic mice that express a constitutively active version of STAT5b, we demonstrate that STAT5 plays a key role in governing B cell development and T cell homeostasis. STAT5 activation leads to a 10-fold increase in pro-B, but not pro-T, cells. Conversely, STAT5 signaling promotes the expansion of mature alphabeta T cells (6-fold increase) and gammadelta and NK T cells (3- to 4-fold increase), but not of mature B cells. In addition, STAT5 activation has dramatically divergent effects on CD8(+) vs CD4(+) T cells, leading to the selective expansion of CD8(+) memory-like T cells and CD4(+)CD25(+) regulatory T cells. These results establish that activation of STAT5 is the primary mechanism underlying both IL-7/IL-15-dependent homeostatic proliferation of naive and memory CD8(+) T cells and IL-2-dependent development of CD4(+)CD25(+) regulatory T cells.

摘要

利用表达组成型活性STAT5b的转基因小鼠，我们证明STAT5在调控B细胞发育和T细胞稳态中起关键作用。STAT5激活导致前B细胞（而非前T细胞）数量增加10倍。相反，STAT5信号传导促进成熟αβ T细胞（增加6倍）以及γδ和NK T细胞（增加3至4倍）的扩增，但不促进成熟B细胞的扩增。此外，STAT5激活对CD8⁺与CD4⁺ T细胞具有显著不同的影响，导致CD8⁺记忆样T细胞和CD4⁺CD25⁺调节性T细胞的选择性扩增。这些结果表明，STAT5激活是幼稚和记忆CD8⁺ T细胞依赖IL-7/IL-15的稳态增殖以及CD4⁺CD25⁺调节性T细胞依赖IL-2发育的主要机制。