Peripheral blood dendritic cell phenotype indicates immune predisposition towards Th-1 responses in human end-stage heart failure

Abstract

Inflammatory reactions may be involved in the late stages of chronic heart failure (CHF). Dendritic cells (DCs) are antigen presenting cells that may play a central role in this process. They consist of myeloid (mDC) and plasmacytoid (pDC) subsets that regulate immunity by polarising naive T-lymphocytes to a Th1 or Th2 response, respectively. We examined the phenotype of peripheral blood total DC, mDC and pDC populations during end-stage heart failure. We compared 18 chronic heart failure patients (age: 54.5 ± 1.8 yrs) to 20 healthy controls (age: 49.1 ± 2.3 yrs). Venous blood was collected prospectively from both groups during a 1 year period. All patients received typical medication against CHF while controls did not use any medication. mDCs (Lin-, HLA-DR+, CD11chigh, CD123low) and pDCs (Lin-, HLA-DR+, CD11clow, CD123high) were measured by flow-cytometry. Subsets 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, the mDC/pDC ratio and the percentage (%) of positive mDCs or pDCs. Values are given in mean ± SEM. CHF patients had more total blood DCs compared to controls (30.3 ± 4.1 vs 15.3 ± 1.4) (p = 0.001) while only the mDC subset was higher than in controls (22.2 ± 4.6 vs 9.3 ± 0.8) (p = 0.002) resulting in a shift of the blood mDC/pDC ratio towards mDCs (from 1.4 ± 0.1 to 2.8 ± 0.7) (p = 0.02). Percentages (%) of both CD83 + mDCs and pDCs were higher in CHF patients compared to controls (CD83 + mDC: 22.2 ± 4.6 vs 12.4 ± 1.8 and CD83 + pDC: 16.9 ± 4.2 vs 3.0 ± 0.5) (p < 0.01). Also % CCR7 + mDCs in CHF patients was higher than in controls (CCR7 + mDC: 28.2 ± 6.7 vs 13.9 ± 2.1;p < 0.01), while % CCR7 + pDCs in patients (73.2 ± 5.9) was no different to controls (68.1 ± 1.9) (p = 0.29). Total DCs are elevated during CHF primarily due to an increase in the mature mDC subset with an elevated homing potential. This suggests systemic inflammation with capability of Th1 polarisation during end-stage heart failure.