Skewed representation of functionally distinct populations of virus-specific CD4 T cells in HIV-1-infected subjects with progressive disease: changes after antiretroviral therapy
Skewed representation of functionally distinct populations of virus-specific CD4 T cells in HIV-1-infected subjects with progressive disease: changes after antiretroviral therapy
复制标题
DOI：
10.1182/blood-2003-04-1203
复制
发表时间：
2004-02-01
期刊：
影响因子：
20.3
通讯作者：
Pantaleo, G
中科院分区：
文献类型：
--
作者：
Harari, A;Petitpierre, S;Pantaleo, G
通过评估血液和淋巴结中抗原特异性刺激后白细胞介素2（IL - 2）和干扰素γ（IFN - γ）分泌细胞的频率，对HIV - 1和巨细胞病毒（CMV）特异性CD4 T细胞介导的抗病毒免疫进行了评估。研究了感染早期患有进行性疾病且无抗逆转录病毒治疗（ART）既往史的HIV - 1感染者、患有非进行性疾病的感染者以及HIV阴性者。根据分泌IL - 2和IFN - γ的能力，确定了3种功能不同的CD4 T细胞群：（1）IL - 2分泌细胞；（2）IL - 2/IFN - γ分泌细胞；（3）IFN - γ分泌细胞。在3个研究组中，CMV特异性CD4 T细胞在3种功能不同的细胞群中几乎均匀分布，非进行性疾病患者中的HIV - 1特异性CD4 T细胞也是如此。然而，在进行性疾病患者中观察到向IFN - γ分泌细胞的偏移（HIV - 1特异性CD4 T细胞的70%），并且几乎没有IL - 2和IL - 2/IFN - γ分泌细胞。IL - 2和IL - 2/IFN - γ分泌的HIV - 1特异性CD4 T细胞的频率与病毒血症水平呈负相关。有趣的是，长期的抗逆转录病毒治疗能够纠正不同HIV - 1特异性CD4 T细胞群的偏移分布，但仅与IL - 2分泌细胞的部分恢复有关。这些结果表明，功能不同的病毒特异性CD4 T细胞群的组成对于病毒控制很重要。
HIV-1- and cytomegalovirus (CMV)-specific CD4 T-cell-mediated antiviral immunity was evaluated by assessing the frequency of interleukin 2 (IL-2)- and interferon gamma (IFN-gamma)-secreting cells following antigen-specific stimulation in blood and lymph node. HIV-1-infected subjects with progressive disease at early stage of infection with no previous history of antiretroviral therapy (ART), subjects with non-progressive disease, and HIV-negative subjects were studied. On the basis of the ability to secrete IL-2 and IFN-gamma, 3 functionally distinct populations of CD4 T cells were identified: (1) IL-2-secreting cells; (2) IL-2/IFN-gamma-secreting cells; and (3) IFN-gamma-secreting cells. CMV-specific CD4 T cells were almost equally distributed within the 3 functionally distinct cell populations in the 3 study groups as well as HIV-1-specific CD4 T cells in subjects with nonprogressive disease. However, a skewing toward IFN-gamma-secreting cells (70% of HIV-1-specific CD4 T cells) was observed in subjects with progressive disease, and IL-2- and IL-2/IFN-gamma-secreting cells were almost absent. The frequencies of IL-2- and of IL-2/IFN-gamma-secreting HIV-1-specific CD4 T cells were negatively correlated with the levels of viremia. Interestingly, prolonged ART was able to correct the skewed representation of different populations of HIV-1-specific CD4 T cells but was associated with only a partial recovery of IL-2-secreting cells. These results indicate that the composition of the pool of functionally distinct virus-specific CD4 T cells is important for virus control.