Athanassopoulos Petros, Vaessen Leonard M B, Balk Aggie H M M, Takkenberg Johanna J M, Maat Alex P W M, Weimar Willem, Bogers Ad J J C
Department of Cardiothoracic Surgery, University Medical Center Rotterdam, Erasmus MC, Rotterdam, The Netherlands.
Eur J Cardiothorac Surg. 2005 May;27(5):783-9. doi: 10.1016/j.ejcts.2004.12.032.
Dendritic cell (DC) mediated allo-antigen presentation to host antigen specific T-lymphocytes initiates acute allograft rejection. We investigated peripheral blood DC (PBDC) incidence and DC subset reconstitution in relation to histological diagnosis of acute cellular rejection (AR) and administration of rejection therapy after clinical heart transplantation (post-HTx).
Venous blood from 20 HTx recipients under standard immunosuppression was collected during serial endomyocardial biopsy (EMB) prior to administration of rejection therapy in a 9-month follow-up post-HTx. Echocardiographic assessment of allograft function during EMB was performed to distinguish clinical necessity for rejection therapy within histologically rejecting patients (R). Myeloid (mDC) and plasmacytoid (pDC) subsets identified by flow-cytometry were analysed for different ISHLT rejection grades. Circulating PBDC incidence and mDC/pDC ratio were compared sequentially between non-rejecting (NR) recipients and R patients treated (3A(+)) or not-treated (3A(-)) with rejection therapy during follow-up.
Eleven samples from biopsy-proven AR episodes (AR(+): ISHLT>or=3) were compared to 89 samples from non-rejection episodes (AR(-): ISHLT grade 0, n=52; grade 1, n=29; grade 2, n=8). We observed an inverse correlation of mDCs (P<0.05) but not pDCs with increasing rejection grade. PBDC incidence and mDC/pDC ratio were low in blood samples obtained during AR (P<0.05 and P<0.01, respectively). Both PBDCs and mDC/pDC ratio decreased during each AR episode (P<0.05). Comparison of 3A(+) and 3A(-) rejectors with NR patients after 12 weeks post-HTx revealed lower PBDC incidence (P<0.01) and mDC/pDC ratio (P<0.05) for R patients, independent of rejection therapy.
Defective DC subset reconstitution by dendritic cell profiling identifies patients at risk for AR after 3 months post-HTx. This finding may contribute to further optimization of immunosuppressive treatment strategies after clinical heart transplantation.
树突状细胞（DC）介导同种异体抗原呈递给宿主抗原特异性T淋巴细胞，引发急性移植排斥反应。我们研究了外周血DC（PBDC）发生率和DC亚群重建与急性细胞排斥反应（AR）的组织学诊断以及临床心脏移植（HTx后）排斥治疗的关系。
在HTx后9个月的随访中，在给予排斥治疗前，对20例接受标准免疫抑制的HTx受者进行系列心内膜心肌活检（EMB）时采集静脉血。在EMB期间对移植心脏功能进行超声心动图评估，以区分组织学上有排斥反应的患者（R）中进行排斥治疗的临床必要性。通过流式细胞术鉴定的髓样（mDC）和浆细胞样（pDC）亚群针对不同的国际心脏和肺移植学会（ISHLT）排斥分级进行分析。在随访期间，比较未发生排斥反应（NR）的受者与接受（3A(+)）或未接受（3A(-)）排斥治疗的R患者之间循环PBDC发生率和mDC/pDC比率。
将11例经活检证实的AR发作样本（AR(+)：ISHLT≥3）与89例非排斥发作样本（AR(-)：ISHLT 0级，n = 52；1级，n = 29；2级，n = 8）进行比较。我们观察到mDCs与排斥分级增加呈负相关（P < 0.05），而pDCs则不然。在AR期间采集的血样中，PBDC发生率和mDC/pDC比率较低（分别为P < 0.05和P < 0.01）。在每次AR发作期间，PBDCs和mDC/pDC比率均下降（P < 0.05）。将HTx后12周的3A(+)和3A(-)排斥者与NR患者进行比较，发现R患者的PBDC发生率（P < 0.01）和mDC/pDC比率（P < 0.05）较低，与排斥治疗无关。
通过树突状细胞分析发现DC亚群重建缺陷可识别HTx后3个月有AR风险的患者。这一发现可能有助于进一步优化临床心脏移植后的免疫抑制治疗策略。
