Immediate major dynamic changes in the T- and NK-cell subset composition after cardiac transplantation

Abstract

Early kinetics of lymphocyte subsets involved in tolerance and rejection following heart transplantation (HTx) are barely defined. Here, we aimed to delineate the early alloimmune response immediately after HTx. Therefore, blood samples from 23 heart-transplanted patients were collected before (pre-), immediately (T0), 24 hours (T24), and 3 weeks (3 wks) after HTx. Immunophenotyping was performed using flow cytometry. A significant increase was detected for terminally differentiated (TEMRA) CD4⁺ or CD8⁺ T cells and CD56^dim CD16⁺ NK cells immediately after HTx linked to a decrease in naïve CD8⁺ and CM CD4⁺ T as well as CD56^bright CD16^- NK cells, returning to baseline levels at T24. More detailed analyses revealed increased CD69⁺ CD25^- and diminished CD69^- CD25^- CD4⁺ or CD8⁺ T-cell proportions at T0 associated with decreasing S1PR1 expression. Passenger T and NK cells were found at low frequencies only in several patients at T0 and did not correlate with lymphocyte alterations. Collectively, these results suggest an immediate, transient shift toward memory T and NK cells following HTx. Opposite migratory properties of naïve versus memory T and NK cells occurring in the early phase after HTx could underlie these observations and may impinge on the development of allo-specific immune responses.

Keywords: Chimerism; NK cells; heart transplantation; naïve and memory T cells; passenger leukocytes.