Division of Immunology, Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, 7925, South Africa.
J Immunol. 2012 Oct 15;189(8):3838-47. doi: 10.4049/jimmunol.1201488. Epub 2012 Sep 10.
The generation of polyfunctional CD8(+) T cells, in response to vaccination or natural infection, has been associated with improved protective immunity. However, it is unclear whether the maintenance of polyfunctionality is related to particular cellular phenotypic characteristics. To determine whether the cytokine expression profile is linked to the memory differentiation stage, we analyzed the degree of polyfunctionality of HIV-specific CD8(+) T cells within different memory subpopulations in 20 antiretroviral therapy-naive HIV-1-infected individuals at ∼34 wk postinfection. These profiles were compared with CMV-specific CD8(+) T cell responses in HIV-uninfected control subjects and in individuals chronically infected with HIV. Our results showed that the polyfunctional abilities of HIV-specific CD8(+) T cells differed according to their memory phenotype. Early-differentiated cells (CD45RO(+)CD27(+)) exhibited a higher proportion of cells positive for three or four functions (p < 0.001), and a lower proportion of monofunctional cells (p < 0.001) compared with terminally differentiated (TD; CD45RO(-)CD27(-)) HIV-specific CD8(+) T cells. The majority of TD HIV-specific CD8(+) T cells were monofunctional (median 69% [interquartile range: 57-83]), producing predominantly CD107a or MIP1β. Moreover, proportions of HIV-specific monofunctional CD8(+) T cells positively associated with proportions of TD HIV-specific CD8(+) T cells (p = 0.019, r = 0.54). In contrast, CMV-specific CD8(+) T cell polyfunctional capacities were similar across all memory subpopulations, with terminally and early-differentiated cells endowed with comparable polyfunctionality. Overall, these data show that the polyfunctional abilities of HIV-specific CD8(+) T cells are influenced by the stage of memory differentiation, which is not the case for CMV-specific responses.
针对疫苗接种或自然感染，多功能 CD8(+) T 细胞的产生与改善的保护性免疫有关。然而，尚不清楚多功能性的维持是否与特定的细胞表型特征有关。为了确定细胞因子表达谱是否与记忆分化阶段有关，我们在 20 名感染 HIV-1 但未接受过抗病毒治疗的个体中，分析了感染后约 34 周时不同记忆亚群中 HIV 特异性 CD8(+) T 细胞的多功能性程度。将这些谱与 HIV 未感染对照者和慢性 HIV 感染者的 CMV 特异性 CD8(+) T 细胞反应进行比较。我们的结果表明，HIV 特异性 CD8(+) T 细胞的多功能能力因记忆表型而异。早期分化细胞（CD45RO(+)CD27(+)）表现出更高比例的三功能或四功能阳性细胞（p<0.001），以及更低比例的单功能细胞（p<0.001），与终末分化（TD；CD45RO(-)CD27(-)）HIV 特异性 CD8(+) T 细胞相比。大多数 TD HIV 特异性 CD8(+) T 细胞为单功能（中位数 69%[四分位距：57-83]），主要产生 CD107a 或 MIP1β。此外，HIV 特异性单功能 CD8(+) T 细胞的比例与 TD HIV 特异性 CD8(+) T 细胞的比例呈正相关（p=0.019，r=0.54）。相比之下，CMV 特异性 CD8(+) T 细胞的多功能能力在所有记忆亚群中相似，终末和早期分化细胞具有相似的多功能性。总的来说，这些数据表明，HIV 特异性 CD8(+) T 细胞的多功能能力受记忆分化阶段的影响，而 CMV 特异性反应则不是。
