PDF(Pubmed)
Abstract：
UNASSIGNED: Cytomegalovirus (CMV) reactivation is a significant concern following allogeneic stem cell transplantation. While previous research has highlighted the anti-CMV reactivation effect of γδ T cells in immunocompromised transplant patients, their characterization in recipients at high risk of CMV reactivation remains limited.
UNASSIGNED: This study focused on D+/R+ recipients (where both donor and recipient are CMV seropositive) at high risk of CMV reactivation. We analyzed 28 patients who experienced CMV recurrence within 100 days post-allogeneic hematopoietic stem cell transplantation, along with 36 matched recipients who did not experience CMV recurrence. Clinical data from both groups were compared, and risk factors for CMV reactivation were identified. Additionally, CMV viral load was measured, and flow cytometric analysis was conducted to assess changes in peripheral blood γδ T cell proportions, subpopulation distribution, and differentiation status. We also analyzed the CDR3 repertoire of the TCR δ chain in different γδ T cell subsets. Functional analysis was performed by measuring the lysis of CMV-infected cells upon stimulation.
UNASSIGNED: CMV reactivation post-transplantation was associated with acute graft-versus-host disease (aGvHD) and reactivation of non-CMV herpesviruses. Notably, CMV reactivation led to sustained expansion of γδ T cells, primarily within the Vδ2neg γδ T cell subpopulation, with a trend toward differentiation from Naive to effector memory cells. Analysis of the δ chain CDR3 repertoire revealed a delay in the reconstitution of clonal diversity in Vδ2neg γδ T cells following CMV reactivation, while Vδ2pos T cells remained unaffected. Upon stimulation with CMV-infected MRC5 cells, the Vδ2neg γδ T cell subpopulation emerged as the primary effector cell group producing IFN-γ and capable of lysing CMV-infected cells. Moreover, our findings suggest that NKG2D is not necessary involved in Vδ2neg γδ T cell-mediated anti-CMV cytotoxicity.
UNASSIGNED: This study provides novel insights into the role of γδ T cells in the immune response to CMV reactivation in transplantation recipients at high risk of CMV infection. Specifically, the Vδ2neg γδ T cell subpopulation appears to be closely associated with CMV reactivation, underscoring their potential role in controlling infection and reflecting CMV reactivation in HSCT patients.
UNASSIGNED: This study focused on D+/R+ recipients (where both donor and recipient are CMV seropositive) at high risk of CMV reactivation. We analyzed 28 patients who experienced CMV recurrence within 100 days post-allogeneic hematopoietic stem cell transplantation, along with 36 matched recipients who did not experience CMV recurrence. Clinical data from both groups were compared, and risk factors for CMV reactivation were identified. Additionally, CMV viral load was measured, and flow cytometric analysis was conducted to assess changes in peripheral blood γδ T cell proportions, subpopulation distribution, and differentiation status. We also analyzed the CDR3 repertoire of the TCR δ chain in different γδ T cell subsets. Functional analysis was performed by measuring the lysis of CMV-infected cells upon stimulation.
UNASSIGNED: CMV reactivation post-transplantation was associated with acute graft-versus-host disease (aGvHD) and reactivation of non-CMV herpesviruses. Notably, CMV reactivation led to sustained expansion of γδ T cells, primarily within the Vδ2neg γδ T cell subpopulation, with a trend toward differentiation from Naive to effector memory cells. Analysis of the δ chain CDR3 repertoire revealed a delay in the reconstitution of clonal diversity in Vδ2neg γδ T cells following CMV reactivation, while Vδ2pos T cells remained unaffected. Upon stimulation with CMV-infected MRC5 cells, the Vδ2neg γδ T cell subpopulation emerged as the primary effector cell group producing IFN-γ and capable of lysing CMV-infected cells. Moreover, our findings suggest that NKG2D is not necessary involved in Vδ2neg γδ T cell-mediated anti-CMV cytotoxicity.
UNASSIGNED: This study provides novel insights into the role of γδ T cells in the immune response to CMV reactivation in transplantation recipients at high risk of CMV infection. Specifically, the Vδ2neg γδ T cell subpopulation appears to be closely associated with CMV reactivation, underscoring their potential role in controlling infection and reflecting CMV reactivation in HSCT patients.
摘要：
■巨细胞病毒（CMV）的再激活是同种异体干细胞移植后的重要问题。虽然先前的研究强调了γδT细胞在免疫受损移植患者中的抗CMV再激活作用，CMV再激活高危受者的特征仍然有限.
■本研究的重点是处于CMV再激活高风险的D+/R+受者（供者和受者均为CMV血清阳性）。我们分析了28例异基因造血干细胞移植后100天内出现CMV复发的患者，以及36名未经历CMV复发的匹配接受者.比较两组的临床数据，并确定了CMV再激活的危险因素。此外,测量CMV病毒载量，并进行流式细胞术分析以评估外周血γδT细胞比例的变化，亚群分布，和差异化地位。我们还分析了不同γδT细胞亚群中TCRδ链的CDR3库。通过在刺激时测量CMV感染的细胞的裂解来进行功能分析。
■移植后CMV的再激活与急性移植物抗宿主病（aGvHD）和非CMV疱疹病毒的再激活有关。值得注意的是,CMV再激活导致γδT细胞持续扩增，主要在Vδ2negγδT细胞亚群内，从幼稚细胞分化为效应记忆细胞的趋势。对δ链CDR3库的分析显示，CMV再激活后Vδ2negγδT细胞中克隆多样性的重建延迟，而Vδ2posT细胞未受影响。在用CMV感染的MRC5细胞刺激时，Vδ2negγδT细胞亚群作为产生IFN-γ并能够裂解CMV感染细胞的主要效应细胞群出现。此外，我们的发现表明，NKG2D不一定参与Vδ2negγδT细胞介导的抗CMV细胞毒性。
■这项研究为γδT细胞在CMV感染高风险的移植受体中对CMV再激活的免疫反应中的作用提供了新的见解。具体来说,Vδ2negγδT细胞亚群似乎与CMV再激活密切相关，强调它们在控制感染和反映HSCT患者CMV再激活方面的潜在作用。
■本研究的重点是处于CMV再激活高风险的D+/R+受者（供者和受者均为CMV血清阳性）。我们分析了28例异基因造血干细胞移植后100天内出现CMV复发的患者，以及36名未经历CMV复发的匹配接受者.比较两组的临床数据，并确定了CMV再激活的危险因素。此外,测量CMV病毒载量，并进行流式细胞术分析以评估外周血γδT细胞比例的变化，亚群分布，和差异化地位。我们还分析了不同γδT细胞亚群中TCRδ链的CDR3库。通过在刺激时测量CMV感染的细胞的裂解来进行功能分析。
■移植后CMV的再激活与急性移植物抗宿主病（aGvHD）和非CMV疱疹病毒的再激活有关。值得注意的是,CMV再激活导致γδT细胞持续扩增，主要在Vδ2negγδT细胞亚群内，从幼稚细胞分化为效应记忆细胞的趋势。对δ链CDR3库的分析显示，CMV再激活后Vδ2negγδT细胞中克隆多样性的重建延迟，而Vδ2posT细胞未受影响。在用CMV感染的MRC5细胞刺激时，Vδ2negγδT细胞亚群作为产生IFN-γ并能够裂解CMV感染细胞的主要效应细胞群出现。此外，我们的发现表明，NKG2D不一定参与Vδ2negγδT细胞介导的抗CMV细胞毒性。
■这项研究为γδT细胞在CMV感染高风险的移植受体中对CMV再激活的免疫反应中的作用提供了新的见解。具体来说,Vδ2negγδT细胞亚群似乎与CMV再激活密切相关，强调它们在控制感染和反映HSCT患者CMV再激活方面的潜在作用。
