Kosmaczewska Agata, Magott-Procelewska Maria, Frydecka Irena, Ciszak Lidia, Bocko Dorota, Szteblich Aleksandra, Kusnierczyk Piotr, Patrzalek Dariusz, Szyber Piotr, Klinger Marian
Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Transpl Immunol. 2006 Jun;16(1):32-40. doi: 10.1016/j.trim.2006.03.007. Epub 2006 Apr 19.
Experimental studies have demonstrated that the intensity of alloreactivity against a transplanted organ results from an interaction of positive (CD40/CD40L and B.7/CD28) and inhibitory (B.7/CTLA-4) signals between antigen-presenting cells (APCs) and T lymphocytes.
We examined the CD40L, CD28, and both surface (s) and intracellular (i) CTLA-4 expressions on freshly drawn and anti-CD3+rIL-2-stimulated peripheral blood CD4+ T cells in groups of kidney transplant recipients in relation to distinct clinical course using the tri-color immunofluorescence method.
The median proportions of freshly isolated CD3+/CD4+/CTLA-4+ and CD3+/CD4+/CD40L+ cells in all groups of graft recipients were higher than in control subjects. In patients with stable graft function (SGF), non-significantly higher sCTLA-4, significantly higher iCTLA-4 expression, and significantly lower CD40L expression on freshly drawn CD4+ T cells compared with recipients with chronic allograft nephropathy (CAN) were found. Moreover, CD4+ T cells from SGF patients showed a higher potential to express sCTLA-4 and CD40L molecules and to down-regulate the CD28 molecule in response to ex vivo stimulation than those from patients with CAN. In patients without acute graft rejection (NAGR), a markedly higher proportion of freshly drawn CD3+/CD4+/iCTLA-4+ cells compared with patients with acute graft rejection (AGR) and an up-regulation of the median percentage of CD3+/CD4+/CD40L+ cells after ex vivo stimulation was found.
In patients with SGF, peripheral blood CD4+ T cells exhibited a higher potential to express surface CTLA-4 and CD40L and to down-regulate CD28 costimulatory molecules in response to ex vivo stimulation, indicating a relationship between the expression patterns of both costimulatory and inhibitory molecules in CD4+ T cells and clinical course after renal transplantation.
实验研究表明，针对移植器官的同种异体反应强度源于抗原呈递细胞（APC）与T淋巴细胞之间正向（CD40/CD40L和B.7/CD28）和抑制性（B.7/CTLA-4）信号的相互作用。
我们采用三色免疫荧光法，研究了肾移植受者组中，新鲜抽取的以及抗CD3+rIL-2刺激后的外周血CD4+T细胞上CD40L、CD28以及表面（s）和细胞内（i）CTLA-4的表达情况，并将其与不同的临床病程相关联。
所有移植受者组中，新鲜分离的CD3+/CD4+/CTLA-4+和CD3+/CD4+/CD40L+细胞的中位数比例高于对照组。与慢性移植肾肾病（CAN）受者相比，移植肾功能稳定（SGF）的患者新鲜抽取的CD4+T细胞上，sCTLA-4略高，iCTLA-4表达显著升高，CD40L表达显著降低。此外，与CAN患者相比，SGF患者的CD4+T细胞在体外刺激后表达sCTLA-4和CD40L分子以及下调CD28分子的潜力更高。在无急性移植排斥反应（NAGR）的患者中，与急性移植排斥反应（AGR）患者相比，新鲜抽取的CD3+/CD4+/iCTLA-4+细胞比例明显更高，并且体外刺激后CD3+/CD4+/CD40L+细胞的中位数百分比上调。
在SGF患者中，外周血CD4+T细胞在体外刺激后表达表面CTLA-4和CD40L以及下调CD28共刺激分子的潜力更高，表明CD4+T细胞中共刺激和抑制分子的表达模式与肾移植后的临床病程之间存在关联。
