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Extracorporeal photopheresis ( ECP) has been used as a prophylactic and therapeutic option to avoid and treat rejection after heart transplantation ( HTx). Tolerance-inducing effects of ECP such as up-regulation of regulatory T cells ( Tregs) are known, but specific effects of ECP on regulatory T cell ( Treg) subsets and dendritic cells ( DCs) are lacking. We analysed different subsets of Tregs and DCs as well as the immune balance status during ECP treatment after HTx. Blood samples were collected from HTx patients treated with ECP for prophylaxis ( n = 9) or from patients with histologically proven acute cellular rejection ( ACR) of grade ≥ 1 B ( n = 9), as well as from control HTx patients without ECP ( HTxC; n = 7). Subsets of Tregs and DCs as well as different cytokine levels were analysed. Almost 80% of the HTx patients showed an effect to ECP treatment with an increase of Tregs and plasmacytoid DCs ( pDCs). The percentage of pDCs before ECP treatment was significantly higher in patients with no ECP effect (26·3% ± 5·6%) compared to patients who showed an effect to ECP (9·8% ± 10·2%; P = 0·011). Analysis of functional subsets of CD4+ CD25high CD127low Tregs showed that CD62 L-, CD120b- and CD147-positive Tregs did not differ between the groups. CD39-positive Tregs increased during ECP treatment compared to HTxC. ECP-treated patients showed higher levels for T helper type 1 ( Th1), Th2 and Th17 cytokines. Cytokine levels were higher in HTx patients with rejection before ECP treatment compared to patients with prophylactic ECP treatment. We recommend a monitoring strategy that includes the quantification and analysis of Tregs, pDCs and the immune balance status before and up to 12 months after starting ECP. [ABSTRACT FROM AUTHOR]

Objectives: Recent studies show that measuring pharmacodynamic (PD) effects offers a unique possibility to predict immunosuppression. Thus, in this study we have monitored the PD properties of immunosuppressants on diverse T-cell functions in heart transplant (HTx) recipients. Materials: PDs and blood concentrations (PK) of three different basis-immunosuppressive drugs were studied: cyclosporin A (CsA); tacrolimus (TRL) and sirolimus (SRL). T-cell function was analysed by expression of proliferating cell nuclear antigen (PCNA) labelling, expression of cytokines (IL-2, IFN-γ) and surface antigen (for example, CD25) by FACS analysis. Results: In group I, at time points C0 and C2, increased CsA-PK significantly inhibited expression of IL-2, IFN-γ, PCNA and CD25 ( P < 0.05). Correlations ( r2) at C2 between inhibition of T-cell functions (PD) with PK and with drug doses were: CsA-PK: 0.71–0.91 and CsA-dose: 0.73–0.87. In group II, increased TRL-PK over time did not further inhibit expression of CD25, but inhibited PCNA expression more on day 3, and IL-2 and IFN-γ expression was significantly higher on days 2 and 3 compared to PD effects of CsA ( P < 0.05). Blood SRL concentrations in C0 group III, increased on day 1 and remained stable at days 3 and 4. Expression of PCNA was not altered in the SRL-PK category, whereas expression of CD25 was higher and expression of cytokines was lower than PD effects of CsA. Conclusions: Our results show that PD effects on T-cell function can be used to monitor immunosuppression bringing potential to increase the efficacy and safety of immunosuppressive therapy after HTx. [ABSTRACT FROM AUTHOR]