Characterization of CD3+CD4-CD8- (double negative) T cells reconstitution in patients following hematopoietic stem-cell transplantation

Abstract

Background: CD3+CD4-CD8-double negative (DN) T cells, as a distinct subset of regulatory T cells (Tregs), played a pivotal role in patients following hematopoietic stem-cell transplantation.

Methods: This study examines the behavior of CD3+CD4-CD8- double negative (DN) T cells in 73 patients at days 30, 60, 90 and 180 after allo-HSCT.

Results: There was no significant difference in neutrophil and platelet engraftment between the higher and lower absolute counts of 30days DN Tregs (p=0.674, 0.863, respectively). The reconstitution of DN Tregs was significantly slower than that of CD8+, CD4+, and CD3+CD8+CD28- T cells (p<0.001), but significantly faster than that of CD19+ and CD4+CD25+ T cells (p<0.001, p=0.032, respectively). Importantly, in the HLA mismatched group, DN Tregs reconstitution had significant effect on aGVHD (p=0.027) and there was significant correlation between aGVHD and DN Tregs reconstitution (p=0.035). DN Tregs reconstitution was significantly faster in the patients who were devoid of aGVHD than that of patients who developed aGVHD. Furthermore, we compared the absolute value of DN Tregs at 30days, 60days, 90days and 180days after allo-HSCT with grade aGVHD and found an inverse linear relationship in the HLA mismatched group (n=37, P<0.001, r=-0.573).

Conclusions: The successful expansion of DN Tregs at 60days after allo-HCST may help avoid severe manifestations of aGVHD in the HLA mismatched group, suggesting that DN Tregs have potential protection effect against aGVHD.