Palmer Brent E, Boritz Eli, Wilson Cara C
Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
J Immunol. 2004 Mar 1;172(5):3337-47. doi: 10.4049/jimmunol.172.5.3337.
An in vitro proliferative defect has been observed in HIV-1-specific CD4(+) T cells from infected subjects with high-level plasma HIV-1 viremia. To determine the mechanism of this defect, HIV-1 Gag-specific CD4(+) T cells from treated and untreated HIV-1-infected subjects were analyzed for cytokine profile, proliferative capacity, and maturation state. Unexpectedly high frequencies of HIV-1-specific, IL-2-producing CD4(+) T cells were measured in subjects with low or undetectable plasma HIV-1 loads, regardless of treatment status, and IL-2 frequencies correlated inversely with viral loads. IL-2-producing CD4(+) T cells also primarily displayed a central memory (T(Cm); CCR7(+)CD45RA(-)) maturation phenotype, whereas IFN-gamma-producing cells were mostly effector memory (T(Em), CCR7(-)CD45RA(-)). Among Gag-specific, IFN-gamma-producing CD4(+) T cells, higher T(Em) frequencies and lower T(Cm) frequencies were observed in untreated, high viral load subjects than in subjects with low viral loads. The percentage of HIV-1 Gag-specific CD4(+) T(Cm) correlated inversely with HIV-1 viral load and directly with Gag-specific CD4(+) T cell proliferation, whereas the opposite relationships were observed for HIV-1-specific CD4(+) T(Em). These results suggest that HIV-1 viremia skews Gag-specific CD4(+) T cells away from an IL-2-producing T(Cm) phenotype and toward a poorly proliferating T(Em) phenotype, which may limit the effectiveness of the HIV-1-specific immune response.
在血浆中HIV-1病毒血症水平较高的感染个体的HIV-1特异性CD4(+) T细胞中，已观察到一种体外增殖缺陷。为了确定这种缺陷的机制，对来自接受治疗和未接受治疗的HIV-1感染个体的HIV-1 Gag特异性CD4(+) T细胞进行了细胞因子谱、增殖能力和成熟状态分析。出乎意料的是，在血浆HIV-1载量低或检测不到的个体中，无论治疗状态如何，均检测到频率异常高的HIV-1特异性、产生IL-2的CD4(+) T细胞，且IL-2频率与病毒载量呈负相关。产生IL-2的CD4(+) T细胞也主要表现为中央记忆（T(Cm)；CCR7(+)CD45RA(-)）成熟表型，而产生IFN-γ的细胞大多为效应记忆（T(Em)，CCR7(-)CD45RA(-)）。在Gag特异性、产生IFN-γ的CD4(+) T细胞中，未治疗、高病毒载量个体的T(Em)频率高于低病毒载量个体，T(Cm)频率低于低病毒载量个体。HIV-1 Gag特异性CD4(+) T(Cm)的百分比与HIV-1病毒载量呈负相关，与Gag特异性CD4(+) T细胞增殖呈正相关，而HIV-1特异性CD4(+) T(Em)则呈现相反的关系。这些结果表明，HIV-1病毒血症使Gag特异性CD4(+) T细胞偏离产生IL-2的T(Cm)表型，转向增殖能力差的T(Em)表型，这可能会限制HIV-1特异性免疫反应的有效性。
