中度/重度免疫抑制的HIV感染儿童：高效抗逆转录病毒治疗后免疫系统的变化
HIV-infected children with moderate/severe immune-suppression: changes in the immune system after highly active antiretroviral therapy.
作者信息
Resino S, Galán I, Pérez A, León J A, Seoane E, Gurbindo D, Muñoz-Fernandez M Angeles
机构信息
Immunobiology Molecular Laboratory, Hospital General Universitario Gregorio Maranón Madrid, Spain.
出版信息
Clin Exp Immunol. 2004 Sep;137(3):570-7. doi: 10.1111/j.1365-2249.2004.02583.x.
The objective of this study was to monitor the changes in the immune system of HIV-infected children with moderate or severe immunodeficiency after highly active antiretroviral therapy (HAART), comprising a follow-up study in 14 HIV-infected children on HAART at two time points separated approximately by 11.8 +/- 0.4 (9.9; 15.4) months. HIV-infected children had significantly lower TREC levels than the control group, but 1 year after HAART the levels increased significantly (P < 0.05). In contrast, viral load (VL) did not change significantly. A positive correlation between T cell receptor excision circle (TREC) levels and both CD4(+) T cell absolute counts (r = 0.558; P = 0.05) and percentages (r = 0.625; P = 0.030) was found. During follow-up on HAART, the percentages and absolute counts of naive CD4(+) and CD8(+) T cell subsets were increased significantly (P < 0.05). CD4(+) CD45RA(hi+) CD62L(+), CD4(+) CD45RA(+) and CD4(+) CD38(+) percentages, and the CD8(+) CD45RA(hi+) CD62L(+) counts reached similar values to the control group. Also, CD8(+) CD45RO(+) CD38(+) and CD8(+) CD45RO(+) percentages, and CD8(+) CD45RO(+) CD38(+) absolute counts (P < 0.05) decreased with respect to the baseline. Lymphoproliferative responses to pokeweed mitogen (PWM) before HAART were lower in HIV-infected children than the control group, but they recovered to normal levels after a year on HAART. Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma production by PHA-activated peripheral blood mononuclear cells (PBMC) was lower before HAART (P < 0.001), but reached similar levels to the control group 1 year after HAART. In HIV-infected children IgG, IgG(1) and IgG(3) plasma levels decreased significantly after HAART. The immune system reconstitution induced by HAART in HIV-infected children seems to be the consequence of decreased immune system activation and naive T cell reconstitution, mainly of thymic origin.
本研究的目的是监测接受高效抗逆转录病毒治疗（HAART）的中度或重度免疫缺陷HIV感染儿童免疫系统的变化，该研究包括对14名接受HAART的HIV感染儿童在两个时间点进行随访，这两个时间点相隔约11.8±0.4（9.9；15.4）个月。HIV感染儿童的TREC水平显著低于对照组，但在HAART治疗1年后，该水平显著升高（P<0.05）。相比之下，病毒载量（VL）没有显著变化。发现T细胞受体切除环（TREC）水平与CD4(+)T细胞绝对计数（r = 0.558；P = 0.05）和百分比（r = 0.625；P = 0.030）均呈正相关。在HAART随访期间，初始CD4(+)和CD8(+)T细胞亚群的百分比和绝对计数显著增加（P<0.05）。CD4(+)CD45RA(hi+)CD62L(+)、CD4(+)CD45RA(+)和CD4(+)CD38(+)百分比，以及CD8(+)CD45RA(hi+)CD62L(+)计数达到与对照组相似的值。此外，CD8(+)CD45RO(+)CD38(+)和CD8(+)CD45RO(+)百分比，以及CD8(+)CD45RO(+)CD38(+)绝对计数相对于基线下降（P<0.05）。HAART治疗前，HIV感染儿童对商陆有丝分裂原（PWM）的淋巴细胞增殖反应低于对照组，但在接受HAART治疗一年后恢复到正常水平。HAART治疗前，PHA激活的外周血单个核细胞（PBMC）产生的肿瘤坏死因子（TNF）-α和干扰素（IFN）-γ较低（P<0.001），但在HAART治疗1年后达到与对照组相似的水平。在HIV感染儿童中，HAART治疗后IgG、IgG(1)和IgG(3)血浆水平显著下降。HAART在HIV感染儿童中诱导的免疫系统重建似乎是免疫系统激活降低和主要来源于胸腺的初始T细胞重建的结果。
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