Shabtai M, Waltzer W C, Dominguez-Rafer C, Pullis C K, Malinowski K, Raisbeck A P, Rapaport F T
Department of Surgery, Health Sciences Center, State University of New York, Stony Brook.
J Urol. 1991 May;145(5):928-31. doi: 10.1016/s0022-5347(17)38493-8.
We describe 12 acute rejection episodes in 11 cadaver donor renal allograft recipients who required OKT3* rescue treatment for steroid-resistant acute rejection (9) or for severe vascular (antibody-mediated) rejection (3). There were 3 treatment failures with subsequent graft loss. Using 2-color flow cytometry the total T (CD3), B (DR+), activated T (CD3DR), T helper/inducer (CD4), T cytotoxic/suppressor (CD8) and activated T cytotoxic cell (CD8DR) subsets were analyzed before, in mid course (5 to 7 days) and at the end of 12 to 14 days of therapy with 5 mg. OKT3 intravenously daily. In parallel changes in the density of such T cell associated antigens were analyzed. Significant decreases in the mean levels of the CD3 (p less than 0.001), CD3DR (p less than 0.05), CD4 (p less than 0.05), CD8 (p less than 0.05) and CD8DR (p less than 0.05) subsets were observed at mid course. A significant decrease in the density of CD3 was observed (p less than 0.0001). The surface antigen density of CD3DR, CD4 and CD8 had decreased by 160% (p less than 0.002), 383% (p less than 0.001) and 260% (p less than 0.001), respectively. At the end of treatment CD3 and CD4 subset levels increased by 425% and 240% (p less than 0.001 and p less than 0.005), respectively. In contrast, the CD3DR and CD8DR subset levels continued to decrease (p less than 0.05). A higher pre-treatment level of CD3DR and a less sharp decrease in CD3, CD4 and CD8 subsets were associated with a higher risk of treatment failure (p less than 0.05, p less than 0.01, p less than 0.05 and p less than 0.05, respectively). The mean decrease in the density of the CD3 marker in the lost grafts was significantly smaller compared to successful outcomes (p less than 0.001). The results of this preliminary study suggest that OKT3 affects T cell associated antigens other than CD3. Such may provide a sensitive prognostic index for the effectiveness of OKT3 therapy, and permit the identification of those patients who might require higher doses and/or duration of OKT3 therapy to enhance renal allograft salvage rates.
我们描述了11例尸体供肾肾移植受者发生的12次急性排斥反应，这些患者因激素抵抗性急性排斥反应（9例）或严重血管性（抗体介导的）排斥反应（3例）而需要OKT3挽救治疗。有3例治疗失败，随后移植肾失功。使用双色流式细胞术分析了总T细胞（CD3）、B细胞（DR +）、活化T细胞（CD3DR）、辅助/诱导性T细胞（CD4）、细胞毒性/抑制性T细胞（CD8）和活化细胞毒性T细胞（CD8DR）亚群，分别在治疗前、疗程中期（5至7天）以及每日静脉注射5mg OKT3治疗12至14天结束时进行分析。同时分析了此类T细胞相关抗原密度的变化。在疗程中期观察到CD3（p < 0.001）、CD3DR（p < 0.05）、CD4（p < 0.05）、CD8（p < 0.05）和CD8DR（p < 0.05）亚群的平均水平显著下降。观察到CD3密度显著降低（p < 0.0001）。CD3DR、CD4和CD8的表面抗原密度分别下降了160%（p < 0.002）、383%（p < 0.001）和260%（p < 0.001）。治疗结束时，CD3和CD4亚群水平分别升高了425%和240%（p < 0.001和p < 0.005）。相比之下，CD3DR和CD8DR亚群水平持续下降（p < 0.05）。治疗前CD3DR水平较高以及CD3、CD4和CD8亚群下降不那么明显与治疗失败风险较高相关（分别为p < 0.05、p < 0.01、p < 0.05和p < 0.05）。与成功结果相比，失功移植肾中CD3标志物密度的平均下降显著更小（p < 0.001）。这项初步研究的结果表明，OKT3除了影响CD3外，还影响T细胞相关抗原。这可能为OKT3治疗的有效性提供一个敏感的预后指标，并有助于识别那些可能需要更高剂量和/或更长疗程的OKT3治疗以提高肾移植挽救率的患者。
