Tugulea S, Ciubotariu R, Colovai A I, Liu Z, Itescu S, Schulman L L, Fisher P E, Hardy M A, Rose E A, Michler R E, Cortesini R, Suciu-Foca N
Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Transplantation. 1997 Sep 27;64(6):842-7. doi: 10.1097/00007890-199709270-00009.
Allograft rejection is mediated by T cells that recognize allogeneic major histocompatibility complex (MHC) molecules via the direct and indirect pathway. The direct pathway involves T cells that react against MHC/peptide complexes expressed on the surface of donor antigen-presenting cells (APCs). In contrast, T cells involved in the indirect pathway recognize peptides derived from processing and presentation of allogeneic MHC molecules by self (recipient) APCs. To explore the relative contribution of these two pathways to rejection, we have evaluated the response of peripheral blood T cells from 50 heart transplant recipients against donor APCs (direct recognition) and against self APCs pulsed with synthetic peptides corresponding to the hypervariable region of the mismatched HLA-DR antigens of the donor (indirect recognition).
T cell reactivity against donor APCs was quantitated by measuring the expression of CD69 on allostimulated CD3+ LDA1+ cells. Reactivity to synthetic allopeptides was determined in limited dilution assays.
Serial studies of the kinetics of direct and indirect recognition showed that both pathways contribute to early acute rejection episodes. Primary rejection was accompanied invariably by indirect recognition of a dominant allopeptide. Intermolecular spreading of T cell epitopes was observed during recurrent rejections. Enhanced recognition of donor alloantigens via the direct pathway was found predominantly during early rejection episodes. A single form of allorecognition was shown to occur in some rejection episodes.
Monitoring of the direct and indirect pathway of allorecognition provides a reliable method for prediction and differential diagnosis of acute rejection of heart allografts.
同种异体移植排斥反应由通过直接和间接途径识别同种异体主要组织相容性复合体（MHC）分子的T细胞介导。直接途径涉及对供体抗原呈递细胞（APC）表面表达的MHC/肽复合物产生反应的T细胞。相比之下，参与间接途径的T细胞识别自身（受体）APC处理和呈递的源自同种异体MHC分子的肽。为了探究这两种途径对排斥反应的相对贡献，我们评估了50名心脏移植受者外周血T细胞对供体APC（直接识别）以及对用与供体错配的HLA-DR抗原高变区对应的合成肽脉冲处理的自身APC（间接识别）的反应。
通过测量异体刺激的CD3 + LDA1 +细胞上CD69的表达来定量T细胞对供体APC的反应性。在有限稀释试验中测定对合成异源肽的反应性。
对直接和间接识别动力学的系列研究表明，这两种途径均促成早期急性排斥反应发作。初次排斥反应总是伴随着对一种显性异源肽的间接识别。在反复排斥反应期间观察到T细胞表位的分子间扩展。主要在早期排斥反应发作期间发现通过直接途径增强了对供体同种异体抗原的识别。在某些排斥反应发作中显示出单一形式的同种异体识别。
监测同种异体识别的直接和间接途径为心脏同种异体移植急性排斥反应的预测和鉴别诊断提供了一种可靠的方法。
