Athanassopoulos Petros, Vaessen Leonard M B, Maat Alex P W M, Balk Aggie H M M, Weimar Willem, Bogers Ad J J C
Department of Cardiothoracic Surgery, Erasmus MC, Rotterdam, The Netherlands.
Eur J Cardiothorac Surg. 2004 Apr;25(4):619-26. doi: 10.1016/j.ejcts.2004.01.032.
Dendritic cells (DCs) are antigen presenting cells that play a central role in inflammation, allograft rejection and immune tolerance. Myeloid (mDC) and plasmacytoid (pDC) subsets regulate immune reactions by polarising naive T-helper cells into a Th1 or Th2 response, respectively. In this study we examined total peripheral blood DCs, mDC and pDC subsets in chronic heart failure (CHF) and clinical heart transplantation (HTx).
We compared 16 heart transplant patients before and after HTx to 14 healthy controls. Whole blood was collected pre-HTx and 1-week post-HTx from patients and at corresponding time-points from controls. All patients received induction and maintenance immunosuppression post-HTx. mDCs and pDCs were measured by flow cytometry and were further characterised for maturation and homing potential to the secondary lymphoid organs with CD83 and CCR7, respectively. Data were expressed as absolute numbers/microl whole blood, percentage (%) mDC or pDC of total blood DCs and % positive DCs for CD83 and CCR7.
CHF patients had more peripheral blood DCs compared to controls (P<0.01) while only the mDC fraction was increased compared to controls (P=0.01). Percentage CD83(+) and CCR7(+) mDCs was also higher than control levels (P<0.05). One week post-HTx, total DCs, mDCs and pDCs decreased below controls (P<0.001). At the same time % mDCs in peripheral blood increased markedly compared to CHF and control levels (P<0.001). The %CD83(+) mDC, %CD83(+) pDC and %CCR7(+) mDC also returned to control levels and only %CCR7(+) pDC decreased below control levels (P=0.005).
Total peripheral blood DCs are elevated during CHF due to an increase in the mature fraction of the mDC subset suggesting a possible Th1 response in end-stage heart failure. The decrease in total DCs and mature mDCs and pDCs seen post-HTx, probably reflects immunological quiescence through adequate immunosuppression. Peripheral blood DC monitoring may provide a new insight into mechanisms of heart failure and allograft rejection by safe weaning from immunosuppression after clinical HTx.
树突状细胞（DCs）是抗原呈递细胞，在炎症、同种异体移植排斥反应和免疫耐受中起核心作用。髓样（mDC）和浆细胞样（pDC）亚群分别通过将初始T辅助细胞极化为Th1或Th2反应来调节免疫反应。在本研究中，我们检测了慢性心力衰竭（CHF）和临床心脏移植（HTx）患者外周血中的总DCs、mDC和pDC亚群。
我们将16例心脏移植患者HTx前后的情况与14名健康对照者进行比较。在HTx前、患者HTx后1周以及对照者的相应时间点采集全血。所有患者在HTx后接受诱导和维持免疫抑制治疗。通过流式细胞术检测mDCs和pDCs，并分别用CD83和CCR7进一步表征其向次级淋巴器官的成熟和归巢潜能。数据以每微升全血中的绝对数量、总血DCs中mDC或pDC的百分比（%）以及CD83和CCR7阳性DCs的百分比表示。
与对照组相比，CHF患者外周血DCs更多（P<0.01），而只有mDC部分与对照组相比增加（P=0.01）。CD83(+)和CCR7(+) mDCs的百分比也高于对照组水平（P<0.05）。HTx后1周，总DCs、mDCs和pDCs降至对照组以下（P<0.001）。与此同时，外周血中mDCs的百分比与CHF和对照组水平相比显著增加（P<0.001）。CD83(+) mDC、CD83(+) pDC和CCR7(+) mDC的百分比也恢复到对照组水平，只有CCR7(+) pDC的百分比降至对照组以下（P=0.005）。
CHF期间外周血总DCs升高是由于mDC亚群成熟部分增加，提示终末期心力衰竭可能存在Th1反应。HTx后总DCs以及成熟的mDCs和pDCs减少，可能反映了通过充分免疫抑制实现的免疫静止。外周血DC监测可能为心力衰竭和同种异体移植排斥反应的机制提供新的见解，通过在临床HTx后安全地减少免疫抑制。
