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艾滋病患者中促炎型 CD161(+) 双阴性(CD3(+)CD4(-)CD8(-))T 细胞的耗竭通过 γδ T 细胞群体的扩增得到改善。

Depletion of pro-inflammatory CD161(+) double negative (CD3(+)CD4(-)CD8(-)) T cells in AIDS patients is ameliorated by expansion of the γδ T cell population.

机构信息

University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, United States.

出版信息

Exp Mol Pathol. 2012 Feb;92(1):155-9. doi: 10.1016/j.yexmp.2011.11.002. Epub 2011 Nov 10.

Abstract

In this present investigation, flow cytometry was utilized to evaluate 13 healthy controls and 31 HIV-1 infected patients who had advanced to the AIDS stage of infection (CD4 count below 200 cells/mm(3)), for the expression of CD161 on CD3(+) double negative (DN) (CD3(+)CD4(-)CD8(-)) T cells, CD4(+) T cells, CD8(+) T cells and γδ T cells. The observed depletion of CD161(+) T cells from peripheral circulation was due primarily to the loss of CD4(+)CD161(+) T cells; as these cells represented 8.67±0.74% of the total healthy control peripheral T cell population, while the CD4(+)CD161(+) T cells of the AIDS group represented only 3.35±0.41% (p=<0.0001) of the total peripheral T cell population. We have also shown here that the DN T cell population was more than doubled in the AIDS group, with the DN T cell population expanding from 3.29±0.45% of the healthy control peripheral T cell population to 8.64±1.16% (p=0.0001) of the AIDS group peripheral T cell population. By evaluating the expression of CD161 on the surface of the DN T cells we showed that within the healthy control group, 47.4±4.99% of the DN T cells were positive for the expression of CD161, while only 26.4±3.54% (p=0.002) of the AIDS group's DN T cells expressed CD161. Despite CD161 expression being halved on the DN T cells of the AIDS group, when we compared the total peripheral T cell percentage of CD161(+) DN T cells between the healthy control group and the AIDS group, there was no statistical difference. Even though only 26.4% DN T cells within the AIDS group were positive for CD161(+), the overall DN T cell population had expanded to such an extent that there was no statistical difference between the groups with regard to CD161(+) DN T cells as a percentage of the total peripheral T cell population. Furthermore, we showed that within the DN T cell population, there was an approximate 2:1 ratio of γδ to αβ T cells, and this ratio was maintained in both the healthy control group and the AIDS group. While evaluating γδ T cells we also discovered that CD8(+) γδ T cells were expanded from 0.62±.09% of the healthy control peripheral T cell population to 5.01±.88% (p=<0.0001) of the peripheral T cell population of the AIDS group; and that this population of CD8(+) γδ T cells underwent the same reduction in percentage of cells expressing CD161(+), further demonstrated that the phenomenon of CD161(+) percentage reduction and compensatory increase in total cell population was affecting the entire circulating γδ T cell population.

摘要

在本研究中,利用流式细胞术评估了 13 名健康对照者和 31 名已进展至艾滋病阶段的 HIV-1 感染者(CD4 计数低于 200 个细胞/mm(3)),评估 CD161 在 CD3(+)双阴性(DN)(CD3(+)CD4(-)CD8(-))T 细胞、CD4(+)T 细胞、CD8(+)T 细胞和 γδ T 细胞上的表达。外周血中 CD161(+)T 细胞的耗竭主要是由于 CD4(+)CD161(+)T 细胞的丢失;因为这些细胞占健康对照组外周 T 细胞群体的 8.67±0.74%,而 AIDS 组的 CD4(+)CD161(+)T 细胞仅占外周 T 细胞群体的 3.35±0.41%(p<0.0001)。我们还表明,AIDS 组的 DN T 细胞群体增加了一倍以上,DN T 细胞群体从健康对照组外周 T 细胞群体的 3.29±0.45%扩展到 AIDS 组外周 T 细胞群体的 8.64±1.16%(p=0.0001)。通过评估 DN T 细胞表面 CD161 的表达,我们表明在健康对照组中,47.4±4.99%的 DN T 细胞表达 CD161,而 AIDS 组的 DN T 细胞中只有 26.4±3.54%(p=0.002)表达 CD161。尽管 AIDS 组的 DN T 细胞上的 CD161 表达减少了一半,但当我们比较健康对照组和 AIDS 组的外周 T 细胞中 CD161(+)DN T 细胞的百分比时,没有统计学差异。尽管 AIDS 组只有 26.4%的 DN T 细胞呈 CD161(+)阳性,但总的 DN T 细胞群体已经扩展到如此程度,以至于两组之间的 DN T 细胞作为外周 T 细胞群体的百分比没有统计学差异。此外,我们表明,在 DN T 细胞群体中,γδ 和 αβ T 细胞之间存在大约 2:1 的比例,并且在健康对照组和 AIDS 组中均保持此比例。在评估 γδ T 细胞时,我们还发现 CD8(+)γδ T 细胞从健康对照组外周 T 细胞群体的 0.62±0.09%扩展到 AIDS 组外周 T 细胞群体的 5.01±0.88%(p<0.0001);并且该 CD8(+)γδ T 细胞群体的 CD161(+)阳性细胞百分比也同样减少,这进一步表明 CD161(+)阳性百分比减少和总细胞群体代偿性增加的现象影响了整个循环 γδ T 细胞群体。

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