Baan Carla C, van der Mast Barbara J, Klepper Mariska, Mol Wendy M, Peeters Annemiek M A, Korevaar Sander S, Balk Aggie H M M, Weimar Willem
Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
Transplantation. 2005 Jul 15;80(1):110-7. doi: 10.1097/01.tp.0000164142.98167.4b.
The transcription factor FOXP3 has been identified as the molecule associated with the regulatory function of CD25+ T cells.
To understand the biology of FOXP3+ T cells in allogeneic reactions, we measured FOXP3 mRNA expression levels in allostimulated CD25 cells and CD25 cells and in peripheral blood mononuclear cells (PBMC). The effect of immunosuppressive drugs on FOXP3 expression was studied in mixed lymphocyte reactions (MLR) in the presence and absence of calcineurin inhibitors (CNI), alphaCD25 mAb, and Rapamycin (Rapa), and analyzed in biopsies from cardiac allograft recipients during acute rejection by quantitative (Q)-PCR.
FOXP3 mRNA expression was restricted to the CD25 population that inhibited the proliferation of allostimulated CD25 cells. In the MLR FOXP3 was readily induced after allostimulation. Kinetic examination of the MLR showed a 10-20-fold higher FOXP3 mRNA expression level after 5 days of culture. The CNI Cyclosporin and Tacrolimus, and alphaCD25 mAb inhibited in vitro induced FOXP3 gene transcription (range 70%-90%), whereas Rapa did not inhibit the induction. After clinical heart transplantation the highest FOXP3 mRNA expression levels were measured in biopsies during acute rejection (P=0.03).
The high FOXP3 mRNA levels during allogeneic responses in vivo and in vitro suggests that regulatory activities of CD25 T cells or the generation of these cells is an intrinsic part of activation. CNI and alphaCD25 mAb in contrast to Rapa, did interfere with this immunosuppressive counter-mechanism and as a result might have an inhibitory effect to tolerance induction after transplantation.
转录因子FOXP3已被确定为与CD25 + T细胞调节功能相关的分子。
为了解FOXP3 + T细胞在同种异体反应中的生物学特性，我们检测了异体刺激的CD25细胞、CD25细胞以及外周血单个核细胞（PBMC）中FOXP3 mRNA的表达水平。在存在和不存在钙调神经磷酸酶抑制剂（CNI）、αCD25单克隆抗体和雷帕霉素（Rapa）的情况下，通过混合淋巴细胞反应（MLR）研究免疫抑制药物对FOXP3表达的影响，并通过定量（Q）-PCR分析心脏移植受者急性排斥反应期间活检组织中的情况。
FOXP3 mRNA表达仅限于抑制异体刺激的CD25细胞增殖的CD25细胞群体。在MLR中，异体刺激后FOXP3很容易被诱导。对MLR的动力学检查显示，培养5天后FOXP3 mRNA表达水平高出10 - 20倍。CNI环孢素和他克莫司以及αCD25单克隆抗体抑制体外诱导的FOXP3基因转录（范围为70% - 90%），而Rapa不抑制这种诱导。临床心脏移植后，急性排斥反应期间活检组织中测得的FOXP3 mRNA表达水平最高（P = 0.03）。
体内和体外同种异体反应期间高FOXP3 mRNA水平表明，CD25 T细胞的调节活性或这些细胞的产生是激活的一个内在部分。与Rapa相比，CNI和αCD25单克隆抗体确实干扰了这种免疫抑制反机制，因此可能对移植后耐受性诱导有抑制作用。
