Roberts M S, Gompels M, Pinching A J, Knight S C
Antigen Presentation Research Group, Clinical Research Centre, Harrow, UK.
AIDS. 1994 Aug;8(8):1097-101. doi: 10.1097/00002030-199408000-00009.
B-cell hyperactivity and hypergammaglobulinaemia with high levels of HIV-1-specific antibody occur during HIV-1 infection. We investigated the role played by antigen-presenting cells (APC) in the ongoing production of antibody.
Adherent monocytes and non-adherent low density dendritic cells were enriched from peripheral blood of patients at different stages of HIV-1 infection (Centers for Disease Control and Prevention categories II, III and IV) and from control subjects at high or low risk of HIV infection. Different concentrations of lymphocytes were cultured in 20 ml hanging drops in the presence or absence of autologous dendritic cells or monocytes. Antibodies to p24 and gp120 were assessed by enzyme-linked immunosorbent assay.
Lymphocytes taken from asymptomatic HIV-1-seropositive subjects and depleted of APC produced low or moderate levels of antibody to gp120 or p24 in vitro. However, adding back autologous dendritic cells significantly enhanced antibody production, although fewer samples showed responses to p24 than to gp120. Less antibody production was stimulated using cells from patients with persistent generalized lymphadenopathy, or if monocytes rather than dendritic cells were added back. Little or no antibody was produced by cells from patients with AIDS and no antibody was detected in cultures of cells from seronegative individuals with low or high risk for infection.
The evidence suggests that ongoing humoral responses to HIV-1 are fuelled by dendritic cells. Thus, the dominance of humoral over cell-mediated responses in HIV-1 infection may depend upon signalling via dendritic cells. Changes in signalling by dendritic cells could be central to the immunologic features of HIV-1 infection.
在HIV-1感染期间会出现B细胞功能亢进和高丙种球蛋白血症，同时伴有高水平的HIV-1特异性抗体。我们研究了抗原呈递细胞（APC）在抗体持续产生过程中所起的作用。
从处于HIV-1感染不同阶段（美国疾病控制与预防中心分类II、III和IV类）的患者外周血以及处于HIV感染高风险或低风险的对照受试者外周血中富集贴壁单核细胞和非贴壁低密度树突状细胞。在有或无自体树突状细胞或单核细胞存在的情况下，将不同浓度的淋巴细胞培养于20 ml悬滴中。通过酶联免疫吸附测定法评估针对p24和gp120的抗体。
从无症状的HIV-1血清阳性受试者中获取的淋巴细胞，去除APC后，在体外产生低水平或中等水平的针对gp120或p24的抗体。然而，添加回自体树突状细胞可显著增强抗体产生，尽管对p24产生反应的样本比对gp120产生反应的样本少。使用来自持续性全身性淋巴结病患者的细胞进行刺激时，抗体产生较少，或者添加回单核细胞而非树突状细胞时也是如此。艾滋病患者的细胞几乎不产生或不产生抗体，并且在来自感染风险高或低的血清阴性个体的细胞培养物中未检测到抗体。
证据表明，对HIV-1的持续体液反应由树突状细胞驱动。因此，在HIV-1感染中体液免疫反应优于细胞介导免疫反应可能取决于通过树突状细胞的信号传导。树突状细胞信号传导的变化可能是HIV-1感染免疫特征的核心。
