*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 CD56^dimCD16⁺ 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 CD56^bright 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.

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