Jagannathan Prasanna, Osborne Christine M, Royce Cassandra, Manion Maura M, Tilton John C, Li Li, Fischer Steven, Hallahan Claire W, Metcalf Julia A, McLaughlin Mary, Pipeling Matthew, McDyer John F, Manley Thomas J, Meier Jeffery L, Altman John D, Hertel Laura, Davey Richard T, Connors Mark, Migueles Stephen A
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1876, USA.
J Virol. 2009 Mar;83(6):2728-42. doi: 10.1128/JVI.02128-08. Epub 2009 Jan 7.
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.
为了更好地理解针对人类免疫缺陷病毒（HIV）的有效免疫反应的组成部分，比较了CD8(+) T细胞对HIV、丙型肝炎病毒（HCV）和巨细胞病毒（CMV）的反应，涉及频率、免疫显性、表型和白细胞介素-2（IL-2）反应性。在表现出对HIV具有持久免疫介导控制的罕见患者（称为长期无进展者（LTNP）或精英控制者）以及进行性HIV感染患者（进展者）中检查了反应。尽管LTNP中针对HIV抗原的增殖能力得以保留，但LTNP和进展者之间针对HIV、CMV和HCV的病毒特异性CD8(+) T细胞反应的强度没有显著差异。与LTNP的HIV特异性CD8(+) T细胞反应相反，CMV pp65中HLA B5701限制性反应很少见，并且不主导总的CMV特异性反应。HIV的病毒特异性CD8(+) T细胞主要为CD27(+)45RO(+)，CMV的为CD27(-)45RA(+)；然而，这些表型高度可变，并且受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，在LTNP和进展者中诱导了CMV特异性CD8(+) T细胞的显著扩增，但相当一部分HIV特异性CD8(+) T细胞的增殖能力并未通过外源性IL-2恢复。这些结果表明，HLA B5701限制性细胞的免疫显性是LTNP中HIV感染所特有的，而不是对其他慢性病毒感染反应的特征。它们还表明，对IL-2反应不佳是进展者的HIV特异性CD8(+) T细胞的特性，这与对维持免疫控制的其他病毒的反应不同。
