Zhang Geoff Y, Hu Min, Wang Yuan Min, Alexander Stephen I
Centre for Kidney Research, Children's Hospital at Westmead, Westmead, New South Wales, Australia.
Curr Opin Organ Transplant. 2009 Feb;14(1):40-5. doi: 10.1097/MOT.0b013e32831da83c.
Foxp3 is the transcription factor that induces the regulatory T cell phenotype. This review will examine issues around Foxp3 induction and function as well as clinical data on tolerance and rejection.
Recent findings have included identification of the signals that drive naive T lymphocytes to express Foxp3 in the thymus and the signals peripherally that induce non-Foxp3 expressing T cells to express FOXP3. Further, the identification of the downstream targets of Foxp3 both by analysis of Foxp3 expressing cells and by analysis of gene promoters that bind Foxp3 has provided new insights into its function. Whereas Foxp3 T regulatory cells (Tregs) are associated with tolerance in a variety of animal transplant models, the human data show expansion of Foxp3 Tregs associated with rejection, though Tregs are also found in transplants in patients with mixed chimerism-induced tolerance. Further, there is a significant difference in the effect of the different immunosuppressive medications on Treg function and expansion that may be important in developing strategies to enhance Tregs in human trials.
Foxp3 CD4 T cells are frequently associated with rejection; however, this does not preclude their protective role and importance in tolerance induction.
Foxp3是诱导调节性T细胞表型的转录因子。本综述将探讨围绕Foxp3诱导和功能的问题以及关于耐受和排斥的临床数据。
最近的发现包括确定了驱动幼稚T淋巴细胞在胸腺中表达Foxp3的信号以及在外周诱导不表达Foxp3的T细胞表达FOXP3的信号。此外，通过对表达Foxp3的细胞进行分析以及对与Foxp3结合的基因启动子进行分析，确定了Foxp3的下游靶点，这为其功能提供了新的见解。虽然Foxp3调节性T细胞（Tregs）在多种动物移植模型中与耐受相关，但人类数据显示，Foxp3 Tregs的扩增与排斥相关，不过在混合嵌合体诱导耐受的患者移植中也发现了Tregs。此外，不同免疫抑制药物对Treg功能和扩增的影响存在显著差异，这在制定人类试验中增强Tregs的策略时可能很重要。
Foxp3 CD4 T细胞常与排斥相关；然而，这并不排除它们在诱导耐受中的保护作用和重要性。
