Comparisons of CD8+ T Cells Specific for Human Immunodeficiency Virus, Hepatitis C Virus, and Cytomegalovirus Reveal Differences in Frequency, Immunodominance, Phenotype, and Interleukin-2 Responsiveness
Comparisons of CD8+ T Cells Specific for Human Immunodeficiency Virus, Hepatitis C Virus, and Cytomegalovirus Reveal Differences in Frequency, Immunodominance, Phenotype, and Interleukin-2 Responsiveness
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DOI：
10.1128/jvi.02128-08
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发表时间：
2009-03-15
影响因子：
5.4
通讯作者：
Migueles, Stephen A.
中科院分区：
文献类型：
--
作者：
Jagannathan, Prasanna;Osborne, Christine M.;Migueles, Stephen A.
为了更好地了解人类免疫缺陷病毒（HIV）有效免疫应答的组成部分，我们比较了CD8(+) t细胞对HIV、丙型肝炎病毒（HCV）和巨细胞病毒（CMV）的频率、免疫优势、表型和白细胞介素-2 （IL-2）应答性。在表现出持久免疫介导的HIV控制的罕见患者（称为长期非进展者（LTNP）或精英控制者）和进行性HIV感染的患者（进展者）中检测了应答。针对HIV、CMV和HCV的病毒特异性CD8(+) t细胞反应的大小在LTNP和进展者之间没有显著差异，尽管它们增殖到HIV抗原的能力仅在LTNP中保留。与LTNP的hiv特异性CD8(+) t细胞应答相反，CMV pp65中HLA b5701限制性应答很少见，并且不占CMV特异性应答的主导地位。病毒特异性CD8(+) T细胞主要是针对HIV的CD27(+) 45RO（+）和针对CMV的CD27(-)45RA(+)；然而，这些表型是高度可变的，并受到病毒血症程度的严重影响。尽管IL-2通过增加进入增殖池的细胞数量和分裂次数，诱导cmv特异性CD8(+) T细胞在LTNP和进展者中显著扩增，但外源性IL-2并没有恢复相当比例的hiv特异性CD8(+) T细胞的增殖能力。这些结果表明，HLA b5701限制性细胞的免疫优势是LTNP中HIV感染的特异性，而不是对其他慢性病毒感染的应答特征。他们还表明，对IL-2的低反应性是hiv特异性CD8（+）进展体T细胞的一个特性，与对其他病毒的免疫控制反应不同。
To better understand the components of an effective immune response to human immunodeficiency virus (HIV), the CD8(+) T-cell responses to HIV, hepatitis C virus (HCV), and cytomegalovirus (CMV) were compared with regard to frequency, immunodominance, phenotype, and interleukin-2 (IL-2) responsiveness. Responses were examined in rare patients exhibiting durable immune-mediated control over HIV, termed long-term nonprogressors (LTNP) or elite controllers, and patients with progressive HIV infection (progressors). The magnitude of the virus-specific CD8(+) T-cell response targeting HIV, CMV, and HCV was not significantly different between LTNP and progressors, even though their capacity to proliferate to HIV antigens was preserved only in LTNP. In contrast to HIV-specific CD8(+) T-cell responses of LTNP, HLA B5701-restricted responses within CMV pp65 were rare and did not dominate the total CMV-specific response. Virus-specific CD8(+) T cells were predominantly CD27(+) 45RO(+) for HIV and CD27(-)45RA(+) for CMV; however, these phenotypes were highly variable and heavily influenced by the degree of viremia. Although IL-2 induced significant expansions of CMV-specific CD8(+) T cells in LTNP and progressors by increasing both the numbers of cells entering the proliferating pool and the number of divisions, the proliferative capacity of a significant proportion of HIV-specific CD8(+) T cells was not restored with exogenous IL-2. These results suggest that immunodominance by HLA B5701-restricted cells is specific to HIV infection in LTNP and is not a feature of responses to other chronic viral infections. They also suggest that poor responsiveness to IL-2 is a property of HIV-specific CD8(+) T cells of progressors that is not shared with responses to other viruses over which immunologic control is maintained.