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Eur J Cardiothorac Surg 2004;25:619-626
© 2004 Elsevier Science NL

Peripheral blood dendritic cells in human end-stage heart failure and the early post-transplant period: evidence for systemic Th1 immune responses

Departments of Cardiothoracic Surgery, Cardiology and Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

Received 14 October 2003; received in revised form 15 January 2004; accepted 21 January 2004.

^* Corresponding author. Address: Department of Cardiothoracic Surgery, Erasmus MC, University Medical Center Rotterdam, Room Ee563a, Dr. Molewaterplein 50, P.O. Box 1738, 3015 GE Rotterdam, The Netherlands. Tel.: +31-10-463-5421; fax: +31-10-408-9443
e-mail: p.athanassopoulos{at}erasmusmc.nl

Objectives: 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). Methods: 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/µl whole blood, percentage (%) mDC or pDC of total blood DCs and % positive DCs for CD83 and CCR7. Results: 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). Conclusions: 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.

Key Words: Blood • Dendritic cells • Heart • Failure • Transplantation

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