Introduction: Tolerance-inducing cell subsets which can support the organ acceptance following heart transplantation (HTx) can be found among dendritic cells (DCs) and regulatory T cells (Tregs). It is assumed that not a single cell population but an interplay between different cell subsets is responsible to avoid rejection following HTx. However, it is unknown which cell subsets change during tolerance induction and maintenance. Therefore, pre-HTx and long-term HTx (LT-HTx; HTx longer than 5 years ago) patients were investigated for their immunological tolerance-inducing profile and their immune balance.

Methods: Heparinized whole blood samples of n=17 patients with end-stage heart failure (pre-HTx) and n=20 LT-HTx patients without rejection episodes were analyzed by flow cytometry for the DC cell subsets expressing BDCA-1, -2, -3, -4 and for the Treg subsets expressing CD39, CD62L, CD120b and CD147. Percentages and mean fluorescence intensities (MFIs) of the cell subsets were documented. The immune balance (IL-2, IL-4, IL-10, IFN-g and IL-17A) was detected by multiplexing using the Luminex 200™.

Results: Age at HTx (pre-HTx: 53.6±12.5yrs, LT-HTx: 46.2±12.9yrs) and at study begin (pre-HTx: 52.2±11.8yrs, LT-HTx: 58.2±14.0yrs) as well as gender (pre-HTx: 87% male, LT-HTx: 92% male) were comparable between both groups. While the total percentage of DCs did not differ between the groups, single DC subsets showed changes between pre-HTx and LT-HTx patients: the myeloid DC markers BDCA-1 and -3 were increased (%BDCA-1+ p=0.02; %BDCA-3+ p=0.09) in LT-HTx patients compared to pre-HTx patients. The total percentage of Tregs and the highly suppressive CD62L+ Treg subset were higher in pre-HTx patients compared to LT-HTx patients (%Tregs p=0.01, %CD62L+ p=0.04). Furthermore, the percentage and expression of CD39+ in Tregs was increased by trend in LT-HTx patients (%CD39+ p=0.06, MFI CD39 p=0.09).

Conclusion: Compared to the immune system prior to HTx, LT-HTx patients without rejection episodes showed a different profile of tolerance-inducing cell subsets: BDCA-1+ and -3+ myeloid DCs, CD62L+ and CD39+ Tregs seem to be the adjustment screws to obtain transplant tolerance and will serve as targets for the development of new tolerance-inducing strategies.

CITATION INFORMATION: Klaeske K, Dieterlen M.-T, Fischer J, Hahn J, Jawad K, Garbade J, Mohr F, Lehmann S. Identification of Promising Targets for Tolerance Induction Following Heart Transplantation. Am J Transplant. 2017;17 (suppl 3).

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