Posselt Andrew M, Vincenti Flavio, Bedolli Melanie, Lantz Marianne, Roberts John P, Hirose Ryutaro
Department of Surgery, University of California, San Francisco, CA 94143-0780, USA.
Transplantation. 2003 Jul 15;76(1):190-5. doi: 10.1097/01.TP.0000073614.29680.A8.
The development of a noninvasive method to diagnose renal allograft rejection could prevent the complications associated with graft biopsy and allow more accurate surveillance of allograft function. The present study determines whether expression of CD69 on peripheral T lymphocytes of renal allograft recipients correlates with the presence of acute graft rejection.
Peripheral blood T lymphocytes from healthy volunteers, renal allograft recipients with elevated creatinine but no evidence of rejection on biopsy, and renal allograft recipients with biopsy-proven rejection were analyzed by flow cytometry for the expression of CD69 and various intracellular cytokines (interleukin-2, interferon-gamma). Results were then compared with the degree of rejection on biopsy.
CD69 expression on CD3+, CD4+, and CD8+ T-cell subsets was low in controls and transplant recipients without allograft rejection. In contrast, patients with renal allograft rejection showed significantly elevated percentages of CD69+ cells in the CD3+ (P<0.01) and CD8+ subsets (P<0.01). The fraction of CD69+ and CD8+ T cells was found to be a more clinically useful test based on receiver-operator characteristics. CD69 expression on CD4+ T cells did not correlate with rejection. Significant intracellular cytokine levels were not detected in unstimulated T cells from any of the groups; stimulation with mitogens increased expression equally among the three groups.
We demonstrate that expression of CD69 on CD3+ and CD8+ peripheral blood T cells correlates closely with the presence of acute graft rejection in renal allograft recipients. Measurement of this surface marker may provide a rapid, noninvasive, and accurate means by which graft rejection can be identified.
开发一种用于诊断肾移植排斥反应的非侵入性方法,可预防与移植肾活检相关的并发症,并能更准确地监测移植肾功能。本研究旨在确定肾移植受者外周血T淋巴细胞上CD69的表达是否与急性移植排斥反应的存在相关。
采用流式细胞术分析健康志愿者、肌酐升高但活检无排斥反应证据的肾移植受者以及活检证实有排斥反应的肾移植受者外周血T淋巴细胞中CD69及多种细胞内细胞因子(白细胞介素-2、干扰素-γ)的表达。然后将结果与活检时的排斥反应程度进行比较。
在对照组和无移植排斥反应的移植受者中,CD3⁺、CD4⁺和CD8⁺T细胞亚群上的CD69表达较低。相比之下,肾移植排斥反应患者的CD3⁺(P<0.01)和CD8⁺亚群(P<0.01)中CD69⁺细胞的百分比显著升高。基于受试者工作特征曲线,发现CD69⁺和CD8⁺T细胞的比例是一项更具临床实用性的检测指标。CD4⁺T细胞上的CD69表达与排斥反应无关。在任何一组未刺激的T细胞中均未检测到显著的细胞内细胞因子水平;用丝裂原刺激后,三组的表达均同等增加。
我们证明,肾移植受者外周血CD3⁺和CD8⁺T细胞上CD69的表达与急性移植排斥反应的存在密切相关。检测这种表面标志物可能提供一种快速、非侵入性且准确的方法来识别移植排斥反应。