CD56^briCD27⁺CD11b^+/- NK Cells Mediated Remission of Agvhd Via Immunoregulation

Background: In our previous study CD56^briCD27⁺CD11b^+/- NK cells show the potential of the remission of aGvHD, while the mechanism behind it is still unknown. Here, three hypothesis have been proposed according to further pilot experiment and literature.

Method: 74 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 CD56^briCD27⁺CD11b^+/- NK cells was performed on rested peripheral blood mononuclear cells (PBMCs) using multiparametric flow cytometry. Furthermore, the western-blot has been performed to determine the expression of HO-1 protein in sorted CD56^briCD27⁺CD11b^+/- NK cells as well.

Result: (1) Our result shows a positive correlation between CD56^briCD27⁺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 CD56^briCD27⁺CD11b^+/- NK cells. Thus we hypothesis that the CD56^briCD27⁺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 CD56^briCD27⁺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 CD56^briCD27⁺CD11b^+/- NK cells. (3) Besides, our work displays that the expression of Heme Oxygenase-1 (HO-1) in CD56^briCD27⁺CD11b^+/- NK cells positively correlated with the secretion of IL-10. Compared with the patients with aGvHD, a higher expression of HO-1 and IL-10 in CD56^briCD27⁺CD11b^+/- NK cells has been found in patients without aGvHD at day 30 after allo-HSCT .

Conclusion: According to these findings, the CD56^briCD27⁺CD11b^+/- NK cells may result in the remission of aGvHD via immunoregulation by regulation of T cells and secretion of IL-10.