免疫复合物和血浆病毒载量与HIV阳性血友病患者CD4 +细胞耗竭、CD8 + DR +和CD16 +细胞计数的关系。对HIV诱导的CD4 +淋巴细胞耗竭免疫发病机制的影响。
Association of immune complexes and plasma viral load with CD4+ cell depletion, CD8+ DR+ and CD16+ cell counts in HIV+ hemophilia patients. Implications for the immunopathogenesis of HIV-induced CD4+ lymphocyte depletion.
作者信息
Daniel V, Süsal C, Weimer R, Zimmermann R, Huth-Kühne A, Opelz G
机构信息
Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Im Neuenheimer Feld 305, D-69120, Heidelberg, Germany.
出版信息
Immunol Lett. 2001 Mar 1;76(2):69-78. doi: 10.1016/s0165-2478(01)00181-x.
OBJECTIVE
There is evidence that HIV induces CD4+ depletion in part by the formation of immune complexes (IC) that attach to CD4+ blood lymphocytes. In the present study we examined the relationship of IC-coated CD4+ blood cells with retroviral replication in HAART-treated patients.
PATIENTS AND METHODS
52 hemophilia patients were studied from 1997 to 1999. Lymphocyte subsets, IgM, IgG and gp120 on CD4+ blood cells, in vitro responses of lymphocytes to mitogens, plasma neopterin and plasma viral load were measured.
RESULTS
Patients with detectable viral replication and without ICs on CD4+ blood lymphocytes had a lower viral load (4100 versus 21000 HIV-1 mRNA copies/ml; P = 0.079) and higher CD4+ cell counts (310/microl versus 161/microl; P = 0.035) than patients with ICs on circulating CD4+ lymphocytes. Among patients with < 80 HIV-1 mRNA copies/ml, IC- individuals had slightly higher CD4+ lymphocyte counts than IC+ patients (384/microl versus 316/microl; n.s.). Further evidence for the clinical relevance of the ICs was obtained when 18 patients who had an undetectable viral load at previous investigations were analyzed. Among patients with a stable undetectable viral load, CD4+ counts increased in 6 of 8 IC- but in none of 2 IC+ individuals. In patients whose viral load increased during the observation period, 5 of 6 IC- but none of 2 IC+ individuals showed higher CD4+ cell counts. Impaired virus killing is suggested by lower CD16+ (35/microl versus 107/microl; P = 0.016), higher CD3+ DR+ (178/microl versus 66/microl; P = 0.006), and higher CD8+ DR+ (142/microl versus 34/microl; P = 0.017) cell counts in IC(-) patients compared to IC- patients without detectable viral load. Strong retroviral replication induced strong T cell dysfunctions. Fewer CD3+ 25+ blood lymphocytes (19/microl versus 47/microl; P = 0.006) and a lower in vitro response of T lymphocytes to the mitogens Con A (RR: 0.3 versus 1.2; P=0.023) and CD3 mab (RR: 0.5 versus 2.4; P = 0.012) was observed in IC+ patients with detectable versus undetectable viral load.
CONCLUSION
Our data suggest that ICs on circulating CD4+ blood lymphocytes are primarily associated with CD4+ lymphocyte depletion whereas the plasma viral load is primarily associated with decreased T lymphocyte activation, lower CD16+ counts, and higher CD8+ DR+ lymphocytes which might be the effector cells for virus elimination.
目的
有证据表明，HIV 部分通过形成附着于 CD4⁺ 血液淋巴细胞的免疫复合物（IC）来诱导 CD4⁺ 细胞耗竭。在本研究中，我们检测了接受高效抗逆转录病毒治疗（HAART）的患者中，IC 包被的 CD4⁺ 血细胞与逆转录病毒复制之间的关系。
患者与方法
1997 年至 1999 年对 52 例血友病患者进行了研究。检测淋巴细胞亚群、CD4⁺ 血细胞上的 IgM、IgG 和 gp120、淋巴细胞对有丝分裂原的体外反应、血浆新蝶呤和血浆病毒载量。
结果
与循环 CD4⁺ 淋巴细胞上有 IC 的患者相比，CD4⁺ 血液淋巴细胞上可检测到病毒复制且无 IC 的患者病毒载量较低（4100 对 21000 HIV-1 mRNA 拷贝/ml；P = 0.079），CD4⁺ 细胞计数较高（310/μl 对 161/μl；P = 0.035）。在 HIV-1 mRNA 拷贝/ml < 80 的患者中，IC⁻ 个体的 CD4⁺ 淋巴细胞计数略高于 IC⁺ 患者（384/μl 对 316/μl；无显著性差异）。对 18 例先前检测病毒载量不可测的患者进行分析时，获得了关于 IC 临床相关性的进一步证据。在病毒载量稳定不可测的患者中，8 例 IC⁻ 患者中有 6 例 CD4⁺ 计数增加，而 2 例 IC⁺ 患者中无一例增加。在观察期内病毒载量增加的患者中，6 例 IC⁻ 患者中有 5 例 CD⁺ 细胞计数升高，而 2 例 IC⁺ 患者中无一例升高。与病毒载量不可测的 IC⁻ 患者相比，IC⁺ 患者 CD16⁺ 细胞计数较低（35/μl 对 107/μl；P = 0.016）、CD3⁺DR⁺ 细胞计数较高（178/μl 对 66/μl；P = 0.006）以及 CD8⁺DR⁺ 细胞计数较高（142/μl 对 34/μl；P = 0.017），提示病毒杀伤受损。强烈的逆转录病毒复制诱导强烈的 T 细胞功能障碍。在病毒载量可测与不可测的 IC⁺ 患者中，观察到 CD3⁺25⁺ 血液淋巴细胞较少（19/μl 对 47/μl；P = 0.006），T 淋巴细胞对有丝分裂原刀豆蛋白 A（RR：0.3 对 1.2；P = 0.023）和 CD3 单克隆抗体（RR：0.5 对 2.4；P = 0.012）的体外反应较低。
结论
我们的数据表明，循环 CD4⁺ 血液淋巴细胞上的 IC 主要与 CD4⁺ 淋巴细胞耗竭有关，而血浆病毒载量主要与 T 淋巴细胞激活降低、CD16⁺ 计数降低以及 CD8⁺DR⁺ 淋巴细胞增多有关，后者可能是病毒清除的效应细胞。
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