CD56briCD27+CD11b+/- NK Cells Mediated Remission of Agvhd Via Immunoregulation

Background: In our previous study, CD56briCD27+CD11b+/- NK cells show the potential of the remission of aGvHD, while the mechanism behind it is still unknown. Thus, in the present study, samples from patient after allo-HSCT within 100 days has been investigated deeply.

Method: 90 samples of patients after allo-HSCT were collected in the affiliated hospital of Guizhou medical university. Immunomonitoring with respect to the phenotype and function of CD56briCD27+CD11b+/- NK cells was performed on rested peripheral blood mononuclear cells (PBMCs) using multiparametric flow cytometry. Furthermore, CD56briCD27+CD11b+/- NK cells have been co-cultured with T cells and ELISPot as well as CFSE staining has been performed to determine the affect of NK cells on T cells. Sorted CD56briCD27+CD11b+/- NK cells have been analyzed by bulk RNA sequencing to elucidate the profile of gene expression. On the other hand, CD56briCD27+CD11b+/- NK cells have been administrated into xgeneic mice agvhd model to observe whether CD56briCD27+CD11b+/- NK cells influence on the onset of aGvHD.

Result: (1) Our result shows a positive correlation between CD56briCD27+CD11b+/- NK cells and Th22, Tfh as well as Th1 like Tfh cells. Interestingly, a dramatic higher expression of homing marker CD62L has been observed on CD56briCD27+CD11b+/- NK cells. Thus we hypothesis that the CD56briCD27+CD11b+/- NK cells may migrate into the lymphoid tissues and regulate the differentiation of naïve T cells. (2) On the other hand, an elevated percentage of NKG2D has been found on CD56briCD27+CD11b+/- NK cells in patients with aGvHD. Meanwhile a high expression of Fas and exhaustion markers have been observed on CD4+ and CD8+ T cells. These results suggest that T cells may be eliminated by CD56briCD27+CD11b+/- NK cells. (3) Both the cytokine secretion and proliferation of T cells has been inhibited by CD56briCD27+CD11b+/- NK cells. (4) CD56briCD27+CD11b+/- NK cells could delay the onset of aGvHD in mice model.

Conclusion: According to these findings, the CD56briCD27+CD11b+/- NK cells may result in the remission of aGvHD via immunoregulation by regulation of T cells.