Pons José A, Revilla-Nuin Beatriz, Baroja-Mazo Alberto, Ramírez Pablo, Martínez-Alarcón Laura, Sánchez-Bueno Francisco, Robles Ricardo, Rios Antonio, Aparicio Pedro, Parrilla Pascual
Division of Gastroenterology and Hepatology, and Liver Transplant Unit, University Hospital Virgen de la Arrixaca (CIBERehd), Murcia, Spain.
Transplantation. 2008 Nov 27;86(10):1370-8. doi: 10.1097/TP.0b013e318188d3e6.
Human liver allografts do sometimes survive in a recipient after withdrawal of immunosuppression (IS), commonly referred to as "operational tolerance." Preliminary clinical data have suggested an increase in the frequency of regulatory T cells (Treg) CD4+CD25 high and FoxP3 expression in operationally tolerant liver transplant recipients (Gr-T). In the context of human liver transplantation, the dynamics of Treg have not been studied. We designed a prospective study to ascertain the profile of the Treg population and FoxP3 expression during IS withdrawal.
To identify such parameters, we analyzed peripheral blood mononuclear cell populations and FoxP3 mRNA expression in 12 liver allograft recipients under cyclosporine A-based IS, who showed stable function of the allograft for more than 2 years.
An increase was observed in the frequency of CD4+CD25 high cells when the IS was withdrawn in Gr-T patients (n=5). These patients exhibited a 3.5-fold increase for relative mRNA FoxP3 expression before the complete IS withdrawal and this continued when IS therapy was stopped. In patients who suffered rejection (n=7) there was no increase in the CD4+CD25 high cells or FoxP3 expression.
With the present study, the first evidence is provided that the increase of CD4+CD25 high T cells and FoxP3 transcripts is associated with operational tolerance in liver transplanted patients during IS withdrawal.
人体肝脏同种异体移植在免疫抑制（IS）撤除后有时能在受者体内存活，通常称为“临床操作性耐受”。初步临床数据表明，临床操作性耐受的肝移植受者（Gr-T）中调节性T细胞（Treg）CD4+CD25高表达及FoxP3表达的频率增加。在人体肝移植背景下，尚未对Treg的动态变化进行研究。我们设计了一项前瞻性研究，以确定IS撤除期间Treg群体特征及FoxP3表达情况。
为确定此类参数，我们分析了12例接受基于环孢素A的IS治疗、同种异体肝移植功能稳定超过2年的受者外周血单个核细胞群体及FoxP3 mRNA表达。
在Gr-T患者（n=5）撤除IS时，观察到CD4+CD25高表达细胞频率增加。这些患者在完全撤除IS前相对mRNA FoxP3表达增加了3.5倍，且在停止IS治疗后仍持续增加。在发生排斥反应的患者（n=7）中，CD4+CD25高表达细胞或FoxP3表达未增加。
本研究首次提供证据表明，CD4+CD25高表达T细胞及FoxP3转录本增加与肝移植患者在IS撤除期间的临床操作性耐受相关。
