Cardiac Transplantation is Accompanied by Major T and NK Cell Alterations within the First 24 Hours
1Institute of Transplant Immunology, Hannover Medical School, Hannover, Germany, 2Division of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany
Meeting: 2020 American Transplant Congress
Abstract number: A-360
Keywords: Heart preservation, Heart/lung transplantation, HLA antigens, Natural killer cells
Session Information
Session Name: Poster Session A: Acute Rejection
Session Type: Poster Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
Location: Virtual
*Purpose: Allogeneic heart transplantation (HTx) displays the only curative approach for terminal heart insufficiency while acute allograft rejection remains a major complication. However, early kinetics of recipient T and NK cells potentially involved in rejection of cardiac allografts have been barely defined. Thus, a detailed dissection of the early T and NK cell dynamics may provide new insights of the immunological mechanisms after HTx.
*Methods: Blood samples from 23 heart transplanted patients treated with a standard of care (SOC) cold preservation or ex-situ heart perfusion (ESHP) were collected before (pre), immediately (T0), 24 h (24h) and 3 weeks (3w) after HTx. Immunephenotyping was performed to delineate T and NK cell subsets and to determine frequencies of donor-derived passenger leucocytes using flow cytometry. Expression of receptors like S1PR1 was quantified by qPCR.
*Results: Directly after HTx, a significant increase in terminally differentiated memory T cells (TEMRA) (CD4+: p<0.001, CD8+: p<0.05) and CD56dimCD16+ NK cells ( p<0.01) was detected, accompanied by a simultaneous decrease in CD8+ naïve (p<0.05), CD4+ central memory (CM) T cells (p<0.0001) and CD56bright CD16– NK cells (p<0.0001), independently from the preservation technique. Notably, these alterations returned to baseline within 24 h. More detailed analyses revealed a diminished T cell proportion of CD69–CD25– (CD4+ p<0.05, CD8+ p<0.001) at T0. In line with the well-known regulatory role of the homing receptor S1PR1, its expression was decreased (p<0.05) in parallel to these dynamic changes. Donor-derived passenger leukocytes were almost undetectable after HTx (mean=2.16%) and did not correlate with the observed T and NK cell alterations.
*Conclusions: Immediately after HTx, patients show dynamic changes in their peripheral T and NK cell subsets resulting in enhanced TEMRA and decreased naïve and CM T cells, which returned to baseline after 24h. Since passenger leukocytes did not contribute to T and NK cell alterations at T0 and a maturation process in such a short time period is unlikely these dynamic changes may have an influence on early allo-immune responses following HTx. These analyses will contribute to a better understanding of the immunological mechanisms involved in the balance between tolerance vs. rejection in HTx.
To cite this abstract in AMA style:
Iske J, Wiegmann B, Ludwig K, Ledwoch N, Chichelnitskiy E, Kühne JF, Hitz A, Bellmàs-Sanz R, Daemen K, Keil J, Ius F, Rochas S, Knoefel A, Haverich A, Warnecke G, Falk CS. Cardiac Transplantation is Accompanied by Major T and NK Cell Alterations within the First 24 Hours [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/cardiac-transplantation-is-accompanied-by-major-t-and-nk-cell-alterations-within-the-first-24-hours/. Accessed November 9, 2024.« Back to 2020 American Transplant Congress