Session Name: Tolerance / Immune Deviation
Session Date & Time: None. Available on demand.
*Purpose: For end-stage lung diseases, lung transplantation (LuTx) is the only curative treatment option. However, acute and chronic rejections are major limitations. Thus, a deeper understanding of the contribution of immune responses early after LuTx is urgently needed. Passenger leukocytes, derived from donor lungs and migrating into the recipients` periphery, are primarily NK and T cells. Our aim was to characterize the expression of killer cell immunoglobulin-like receptors (KIR), regulating NK and CD8+ T cell activity, on donor and recipient NK and T cells in recipient blood after LuTx. Moreover, we investigated the functional capacity of donor vs. recipient NK cells.
*Methods: Peripheral blood samples at pre, T0hr, T24hrs and 3wks post Tx of n=51 LuTx recipients were analyzed for the presence of HLA-mismatched donor cells and their KIR repertoire as well as activation status using flow cytometry. These results were correlated with clinical parameters, i.e. primary graft dysfunction (PGD) and cold ischemic times (CIT).
*Results: Within the first 3wks after LuTx, donor NK and T cells were detected in n=51 patients with a peak at T0hr. An increase of the KIR2DL1-positive subset was detected within the donor NK cell repertoire. Moreover, donor NK cells showed significantly higher frequencies of KIR2DL1-positive cells (p<0.01) 3wks post LuTx compared to recipient NK cells. This effect was also observed in donor T cells 3wks after LuTx with higher proportions of KIR2DL1- (p<0.05) and KIR3DL1- (p<0.01) positive T cells. Higher activation levels of donor NK and T cells (p<0.001) were detected as compared to recipient cells via CD25 expression as well as enhanced degranulation capacity upon activation by K562 target cells. The KIR repertoire on donor NK and T cells in LuTx recipient blood does not correlate with PGD, while the frequencies of KIR+ donor NK cells increased directly after LuTx with longer CIT.
*Conclusions: Higher frequencies of donor NK and T cells expressing KIR compared to recipient NK and T cells argue for their origin in the lung as part of a highly specialized immunocompetent compartment. Despite KIR expression, the activation level of donor NK and T cells in the periphery of the recipient may be higher compared to recipient cells. Moreover, a positive correlation was detected for KIR surface expression on NK cells and CIT but not PGD implying extended preservation times have an impact on the NK subset composition. Hence, donor NK and T cells might have a regulatory effect in the balance between tolerance and rejection as well as graft survival after LuTx.
To cite this abstract in AMA style:Kühne JF, Hitz A, Bläsing KA, Wiegmann B, Sanz RBellmàs, Ius F, Haverich A, Warnecke G, Falk CS. Donor Lymphocytes in Peripheral Blood of Patients After Lung Transplantation Comprise High Frequencies of Killer Cell Immunoglobulin-like Receptor-positive T and NK Cell Subsets [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-lymphocytes-in-peripheral-blood-of-patients-after-lung-transplantation-comprise-high-frequencies-of-killer-cell-immunoglobulin-like-receptor-positive-t-and-nk-cell-subsets/. Accessed June 11, 2021.
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