Das Spenderalter beeinflusst die Immunantwort nach Organtransplantation.

Advanced donor age may be associated with an altered immune response of the recipient. We investigated underlying causes of an increased immunogenicity with advanced donor age and analyzed the immune response in a chronic mouse heart transplant model. Age dependent changes in naive hearts and heart allografts from 3, 12 and 18 mths old donors were examined. Elderly, non-manipulated hearts contained overall significantly elevated frequencies of CD4⁺ and CD8⁺ T-cells and Dendritic Cells (DC) (p < 0.05). While survival rates were comparable between all groups, numbers of activated DCs (CD11c⁺I-A^b+) and NK cells had significantly increased in recipient spleens after transplantation of 18mths old heart grafts at day 14. In parallel, frequencies of effector/memory phenotype T-cells and IFNg⁺CD4⁺ T-cells were significantly elevated indicating an enhanced innate immune and memory T-cell activation. In contrast, proliferation as measured by Mixed Lymphocyte Reaction (MLR; p = 0.0002) and CD4⁺ T-cells expressing IL-2 was decreased. Likewise, T-cell activation (CD69 and CD25) was significantly delayed. At 8 weeks, recipients of old grafts demonstrated significantly higher frequencies of activated CD4⁺ and CD8⁺ T-cells and activated DCs (p < 0.05). At the same time, proliferation (MLR) and alloreactive IFNg-production significantly inclined with increasing donor age (p < 0.01). Immunohistochemical staining showed enhanced CD11c⁺ infiltrates in 18mths old heart graft. Surprisingly, fewer CD4⁺ and CD8⁺ T-cells were detected with increasing donor age while frequencies of regulatory T-cells in old hearts were enhanced. Intragraft gene expression of Fas and FasL was significantly elevated; TUNEL staining of graft infiltrating T-cells confirmed an enhanced apoptosis with increasing donor age (p < 0.05). These results emphasize an intensified early immune response towards organs from old donors. [ABSTRACT FROM AUTHOR]