Date: Tuesday, May 5, 2015
Session Name: Poster Session D: Innate Immunity in Transplantation
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
The role of NK cells in either graft rejection or tolerance induction is still discussed controversially. In order to clarify the effect of long-term immunosuppression on NK cells, we compared the residual function of NK cells derived from kidney transplant (KTx) recipients under immunosuppression with NK cell function of healthy donors.
PBMC of healthy donors (n=4) or kidney recipients (n=4) were co-incubated for 18h with K562 target cells, resembling NK cell-specific stimulation. IFN-g production was quantified by ELISpot-technique, supernatants were analyzed for perforin and granzyme A/B secretion by multiplex assays. PBMC of healthy donors (n=6) or kidney recipients (n=4) were stimulated for 24 hours with PMA/Ionomycin and analyzed by flow cytometry, supernatants were harvested and analyzed to determine secretion of Th1/Th2/Th17 and Th22 cytokines.
NK cells of kidney transplant recipients secreted substantially less IFN-g after specific stimulation with K562 target cells. In contrast, the cytotoxin content of lytic granules seemed to be unaffected by immunosuppression in patients because perforin and granzyme A/B release was comparable to healthy donors. PMA/Ionomycin-stimulated PBMC of KTx patients and healthy donors showed equal IFN-g secretion associated with down-regulation of CD16. However, other NK cell-derived cytokines such as IL-22, Il-17A, TNF-a and IL-31 were significantly decreased compared to healthy donors.
The capacity of NK cells to produce cytokines is reduced in KTx patients after long-term immunosuppressive treatment. The residual capacity to produce IFN-g seems to be dependent on the stimulus: the general capability of NK cells for IFN-g production is not impaired in KTx patients, while response to specific stimulation by HLA-class-I-negative target cells was significantly reduced, similar to production of other NK cell-derived cytokines. Thus, immunosuppressive treatment with Calcineurin inhibitors may alter NK cell phenotype and cytokine production permanently, while NK cytotoxicity cannot be controlled by this immunosuppressive regimen.
To cite this abstract in AMA style:Hoffmann U, Neudoerfl C, Daemen K, Keil J, Blume C, Lehner F, Haller H, Falk C. NK Cells of Kidney Transplant Recipients Show a Reduced Capacity to Produce Cytokines But Retain Their Cytotoxic Capacity [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/nk-cells-of-kidney-transplant-recipients-show-a-reduced-capacity-to-produce-cytokines-but-retain-their-cytotoxic-capacity/. Accessed October 31, 2020.
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