Early Everolimus Initiation Fails to Counteract the Cytotoxic Response Mediated by CD8 T and NK Cells in Heart Transplant Patients.

The positive long-term effects of conversion to everolimus (EVL) after heart transplantation (HT) have been evaluated in several studies. However, the timing of EVL initiation, the best way to combine it with other immunosuppressive treatments, and the impact of these combinations on the immune response are poorly understood aspects. Here, we analyzed the immune phenotype and function of HT patients ( = 56) at short and long terms (prospective and retrospective cohorts), taking into account the time of EVL initiation: early (3 months post-transplant, EVL-E group) or late (>1 year post-transplant, EVL-L group) compared with mycophenolate mofetil treatment (MMF group).

DNA demethylation and histone H3K9 acetylation determine the active transcription of the NKG2D gene in human CD8+ T and NK cells.

The human activating receptor NKG2D is mainly expressed by NK, NKT, γδ T and CD8(+) T cells and, under certain conditions, by CD4(+) T cells. This receptor recognizes a diverse family of ligands (MICA, MICB and ULBPs 1-6) leading to the activation of effector cells and triggering the lysis of target cells. The NKG2D receptor-ligand system plays an important role in the immune response to infections, tumors, transplanted graft and autoantigens.