Kassu Afework, D'Souza Michelle, O'Connor Brian P, Kelly-McKnight Elizabeth, Akkina Ramesh, Fontenot Andrew P, Palmer Brent E
Division of Allergy and Clinical Immunology, Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
Clin Immunol. 2009 Aug;132(2):234-45. doi: 10.1016/j.clim.2009.03.531. Epub 2009 Apr 29.
CD4+ T cell dysfunction in subjects with chronic HIV infection is in part due to an imbalance of costimulatory and coinhibitory receptors. We report that virus-specific CD4+ T cells expressing 4-1BB (CD137) or OX40 (CD134) produced more IL-2 than cells lacking these costimulatory receptors (P<0.05) and that 4-1BB was expressed at a lower level on HIV- than CMV-specific IFN-gamma and IL-2 producing CD4+ T cells (P<0.0001 and P<0.01, respectively). Suppression of viral replication with antiretroviral therapy was associated with increased 4-1BB expression on HIV- and CMV-specific IL-2 producing CD4+ T cells (P<0.05 and P<0.01, respectively) and the percentage of IL-2 producing HIV-specific CD4+ T cells that expressed 4-1BB was inversely correlated with HIV plasma viral load (r=-0.75, P=0.007). These findings indicate that the loss of 4-1BB on HIV-specific CD4+ T cells is associated with viral replication and that it may contribute to reduced IL-2 production observed during chronic infection.
慢性HIV感染患者中CD4+ T细胞功能障碍部分归因于共刺激和共抑制受体的失衡。我们报告称，表达4-1BB（CD137）或OX40（CD134）的病毒特异性CD4+ T细胞比缺乏这些共刺激受体的细胞产生更多的IL-2（P<0.05），并且在HIV特异性而非巨细胞病毒（CMV）特异性产生IFN-γ和IL-2的CD4+ T细胞上，4-1BB的表达水平更低（分别为P<0.0001和P<0.01）。抗逆转录病毒疗法抑制病毒复制与HIV特异性和CMV特异性产生IL-2的CD4+ T细胞上4-1BB表达增加相关（分别为P<0.05和P<0.01），并且表达4-1BB的HIV特异性产生IL-2的CD4+ T细胞百分比与HIV血浆病毒载量呈负相关（r=-0.75，P=0.007）。这些发现表明，HIV特异性CD4+ T细胞上4-1BB的缺失与病毒复制相关，并且可能导致慢性感染期间观察到的IL-2产生减少。
