Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*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 March 3, 2021.
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