Circulating Donor T and NK Cells in Lung Transplantation Recipients Are Derived from the Donor Lung Parenchyma and Represent Tissue-Resident Memory Cells
1Institute of Transplant Immunology, Hannover Medical School (MHH), Hannover, Germany, 2Department for Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School (MHH), Hannover, Germany, 3Institute of Pathology, Hannover Medical School (MHH), Hannover, Germany
Meeting: 2019 American Transplant Congress
Abstract number: 577
Keywords: Ischemia, Lung transplantation, Natural killer cells, T cells
Session Information
Date: Tuesday, June 4, 2019
Session Name: Concurrent Session: Lymphocyte Biology: Signaling, Co-Stimulation, Regulation
Session Time: 4:30pm-6:00pm
Presentation Time: 5:42pm-5:54pm
Location: Room 311
*Purpose: We previously identified donor lymphocytes in peripheral blood of recipients directly after transplantation and persisting at least three weeks that were characterized by the tissue retention marker CD69. In order to determine their origin, we hypothesized that donor T and NK cells have a peculiar tissue-resident memory phenotype that is shared between cells derived from lung perfusates, trachea, parenchyma and lymph nodes (LN).
*Methods: Donor lymphocytes in recipient blood were determined in 27 lung recipients at T0, T24, 3 weeks by staining of donor HLA class I molecules in combination with lineage- and tissue-specific markers using FACS. The phenotype of T and NK cells in perfusates (n=30), donor trachea (n=5), LN (n=10) and recipient explanted parenchyma (n=15) was compared to circulating cells using the same markers.
*Results: In peripheral blood of all lung recipients, donor T and NK cells were detected at T0, T24 and 3 weeks and had higher CD69 expression compared to recipient cells (p=0.001 to 0.03) and were mostly CD25–. This phenotype was similar to T and NK cells in corresponding perfusates, with significantly increased CD69 expression compared to circulating PBMCs (all p<0.005) without CD25 expression. NK cells from donor perfusate and tracheas were CD56dim CD16+, in contrast to lung-draining LN that only possess CD56bright CD16– NK cells. T cells from trachea and LN showed also high CD69 expression and a significant enrichment of effector memory (CCR7– CD45RO+) T cells (all p<0.03). In donor trachea and recipient parenchyma, CD69+ T cells showed coexpression of other tissue residency markers such as CD103, CD49a and PD-1, while these were not found in perfusates, highlighting differences between these compartments.
*Conclusions: Our results suggest that donor T and NK cells found in the periphery of lung transplant recipients are derived from lung parenchyma and represent tissue-resident memory cells. This transient chimerism in recipient blood might carry clinically relevant implications for the induction of tolerance and immunity after transplantation.
To cite this abstract in AMA style:
Kuehne JF, Sanz RBallmàs, Hitz A, Wiegmann B, Bläsing KA, Ius F, Knoefel A, Tudorache I, Avsar M, Jonigk D, Haverich A, Warnecke G, Falk C. Circulating Donor T and NK Cells in Lung Transplantation Recipients Are Derived from the Donor Lung Parenchyma and Represent Tissue-Resident Memory Cells [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/circulating-donor-t-and-nk-cells-in-lung-transplantation-recipients-are-derived-from-the-donor-lung-parenchyma-and-represent-tissue-resident-memory-cells/. Accessed September 29, 2020.« Back to 2019 American Transplant Congress