RESUMO
Whereas innate immune cells, such as NK and innate lymphoid cells (ILCs), have been characterized in different human tissues, knowledge on the thymic CD56-expressing cell subsets is limited. In this study, the rare subpopulations of thymic CD56+CD3- cells from samples of >100 patients have been successfully analyzed. The results revealed fundamental differences between thymic and peripheral blood (PB) CD56+CD3- cells. Thymic tissues lacked immunoregulatory CD56highCD16dim NK cells but showed two Eomes+CD56dim subsets on which common NK cell markers were significantly altered. CD56dimCD16high cells expressed high amounts of NKG2A, NKG2D, and CD27 with low CD57. Conversely, CD56dimCD16dim cells displayed high CD127 but low expression of KIR, NKG2D, and natural cytotoxicity receptors (NCRs). Thymic CD56+CD3- cells were able to gain cytotoxicity but were especially immunoregulatory cells, producing a broad range of cytokines. Finally, one population of thymic CD56+ cells resembled conventional NK cells, whereas the other represented a novel, noncanonical NK subset.
Assuntos
Antígeno CD56/análise , Células Matadoras Naturais/imunologia , Subpopulações de Linfócitos/imunologia , Timo/imunologia , Adulto , Envelhecimento/imunologia , Antígenos CD/análise , Degranulação Celular , Separação Celular , Criança , Citocinas/biossíntese , Citotoxicidade Imunológica , Citometria de Fluxo , Humanos , Imunofenotipagem/métodos , Células Matadoras Naturais/classificação , Microscopia Confocal , Microscopia de Fluorescência , Receptores de Células Matadoras Naturais/análise , Timo/citologia , Timo/crescimento & desenvolvimentoRESUMO
One of the major challenges of allogeneic stem cell transplantation (allo-SCT) is to reduce the risk of graft-versus-host disease (GVHD) while boosting the graft-versus-leukemia (GVL) effect. The reconstitution of natural killer (NK) cells following allo-SCT is of notable interest due to their known capability to induce GVL without GVHD. Here, in this study, we investigate the association between the incidence and severity of acute graft-versus-host disease (aGVHD) and the early reconstitution of NK cell subsets following allo-SCT. We analyzed 342 samples from 107 patients using flow cytometry, with a focus on immature CD56high and mature cytotoxic CD56dim NK cells. Longitudinal analysis of immune reconstitution after allo-SCT showed that the incidence of aGVHD was associated with a delayed expansion of the entire NK cell population, in particular the CD56high subset. Notably, the disturbed reconstitution of the CD56high NK cells also correlated with the severity of aGVHD.