CD28 down-regulation on CD4 T cells is a marker for graft dysfunction in lung transplant recipients.
CD28 down-regulation on CD4 T cells is a marker for graft dysfunction in lung transplant recipients.
复制标题
CD4 T 细胞上的 CD28 下调是肺移植受者移植物功能障碍的标志。
DOI：
10.1164/rccm.200701-013oc
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发表时间：
2008
影响因子：
24.7
通讯作者：
Duncan,StevenR
中科院分区：
文献类型：
--
作者：
Studer,SeanM;George,MPatricia;Zhu,Xuehai;Song,Yifang;Valentine,VincentG;Stoner,MichaelW;Sethi,Jigme;Steele,Chad;Duncan,StevenR
Rationale: Repeated antigen-driven proliferations cause CD28 on T cells to down-regulate. We hypothesized that alloantigen-induced proliferations could cause CD28 down-regulation in lung transplant recipients.Objectives: To ascertain if CD28 down-regulation on CD4 T cells associated with manifestations of allograft dysfunction in lung transplant recipients.Methods: Peripheral blood CD4 T cells from 65 recipients were analyzed by flow cytometry, cytokine multiplex and proliferative assays, and correlated with clinical events.Measurements and Main Results: Findings that CD28 was present on less than 90% of total CD4 T cells were predominantly seen among the recipients with bronchiolitis obliterans syndrome (specificity = 88%). Perforin and granzyme B were produced by >50% of the CD4+CD28nullcells, but less than 6% of autologous CD4+CD28+cells (P< 0.006). CD4+CD28nullcells also had increased productions of proinflammatory cytokines, but less frequently expressed regulatory T-cell marker FoxP3 (2.1 ± 1.3%), compared with autologous CD4+CD28+(9.5 ± 1.4;P= 0.01). Cyclosporine A (100 ng/ml) inhibited proliferation of CD4+CD28nullcells by 33 ± 11% versus 68 ± 12% inhibition of CD4+CD28+(P= 0.025). FEV1fell 6 months later (0.35 ± 0.04 L) in recipients with CD4+CD28+/CD4totalless than 90% (CD28% Low) compared with 0.08 ± 0.08 L among CD4+CD28+/CD4total(CD28% High) greater than 90% (CD28% High) recipients (P= 0.013). Two-year freedom from death or retransplantation in CD28% Low recipients was 32 ± 10% versus 78 ± 6% among the CD28% High subjects (P< 0.0001).Conclusions: CD28 down-regulation on CD4 cells is associated with bronchiolitis obliterans syndrome and poor outcomes in lung transplantation recipients. CD4+CD28nullcells have unusual, potentially pathogenic characteristics, and could be important in the progression of allograft dysfunction. These findings may illuminate a novel paradigm of transplantation immunopathogenesis, and suggest that CD28 measurements could identify recipients at risk for clinical deteriorations.
