Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA.
PLoS One. 2009 Aug 11;4(8):e6580. doi: 10.1371/journal.pone.0006580.
Signaling through the T cell antigen receptor (TCR) is important for the homeostasis of naïve and memory CD4(+) T cells. The significance of TCR signaling in regulatory T (Treg) cells has not been systematically addressed. Using an Ox40-cre allele that is prominently expressed in Treg cells, and a conditional null allele of the gene encoding p56(Lck), we have examined the importance of TCR signaling in Treg cells. Inactivation of p56(Lck) resulted in abnormal Treg homeostasis characterized by impaired turnover, preferential redistribution to the lymph nodes, loss of suppressive function, and striking changes in gene expression. Abnormal Treg cell homeostasis and function did not reflect the involvement of p56(Lck) in CD4 function because these effects were not observed when CD4 expression was inactivated by Ox40-cre.The results make clear multiple aspects of Treg cell homeostasis and phenotype that are dependent on a sustained capacity to signal through the TCR.
T 细胞抗原受体 (TCR) 的信号转导对于初始和记忆 CD4(+) T 细胞的稳态至关重要。TCR 信号在调节性 T (Treg) 细胞中的意义尚未得到系统的解决。使用在 Treg 细胞中显著表达的 Ox40-cre 等位基因和编码 p56(Lck) 的基因的条件性缺失等位基因，我们研究了 TCR 信号在 Treg 细胞中的重要性。p56(Lck)的失活导致 Treg 稳态异常，表现为周转率受损、优先向淋巴结重新分布、抑制功能丧失以及基因表达的显著变化。Treg 细胞稳态和功能的异常并不反映 p56(Lck)参与 CD4 功能，因为当 Ox40-cre 使 CD4 表达失活时，没有观察到这些效应。这些结果明确了 Treg 细胞稳态和表型的多个方面，这些方面依赖于通过 TCR 进行持续信号转导的能力。
