关键词: γδ T细胞, 造血干细胞移植, 巨细胞病毒, 病毒再激活

Abstract:

Objective To analyze the relationship between peripheral blood γδ T cells and cytomegalovirus （CMV） reactivation in recipients undergoing allogeneic hematopoietic stem cell transplantation（allo-HSCT）. Methods A total of 64 allo-HSCT patients from Ruijin Hospital，Shanghai Jiao Tong University School of Medicine from January 2023 to June 2023 were enrolled and followed for 1 year. Based on the presence of CMV viremia，the patients were classified into CMV reactivation group（28 cases，including 6 with refractory CMV infection）and CMV negative group（36 cases）. Totally，32 healthy adult donors were enrolled as healthy control group. The clinical data were collected. Peripheral blood γδ T cell proportions，subset distribution，differentiation status and interferon-gamma（IFN-γ） expression were analyzed alongside CMV DNA load in all the subjects. Results The incidence of acute graft-versus-host disease（GvHD）and non-cytomegalovirus herpesvirus （NCH） reactivation was higher in CMV reactivation group than that in CMV negative group（P<0.05），with no statistical significance in the other clinical parameters（P>0.05）. The proportions of γδ T cells and Vδ2− γδ T cells were higher in CMV reactivation group compared to CMV negative and healthy control groups（P<0.05）. Post-reactivation γδ T cell and Vδ2− γδ T cell proportions were increased compared to pre-reactivation stage（P<0.01）. In 6 refractory CMV infection cases，γδ T cell and Vδ2− γδ T cell proportions increased rapidly and persistently from viremia onset until 2 weeks after clearance. The CMV reactivation group showed significant differences in naive and CD45RA+ effector memory RA+（EMRA）cell proportions among γδ T cells，naive and effector memory（EM）cells in Vδ2− γδ T cells，central memory（CM）and EM cell proportions in Vδ2- γδ T cells compared to CMV negative group（P<0.05）. Co-culture of peripheral blood mononuclear cells（PBMC）with CMV-infected MRC5 cells demonstrated that the Vδ2− subset had a stronger capacity for IFN-γ secretion compared to Vδ2+γδ T cell subsets. Conclusions γδ T cells，particularly the Vδ2−γδ T cell subsets，are associated with CMV reactivation in allo-HSCT patients and produce high levels of the effector molecule IFN-γ. Vδ2− γδ T cell subset may serve as a biomarker for CMV reactivation and clearance.

Key words: γδ T cell, Hematopoietic stem cell transplantation, Cytomegalovirus, Viral reactivation