Troye-Blomberg M, Andersson G, Stoczkowska M, Shabo R, Romero P, Patarroyo M E, Wigzell H, Perlmann P
J Immunol. 1985 Nov;135(5):3498-504.
T cells from patients acutely infected with malaria exhibit a disease-related stimulation of DNA synthesis in response to Plasmodium falciparum antigen in vitro. This response is weak and short-lived, suggestive of induction of suppressor mechanisms. Exogenous T cell growth factor (IL 2) that was added to antigen-stimulated T cell cultures enhanced proliferation in antigen-responsive cultures, indicating that the lymphocytes expressed IL 2 receptors. In contrast, the addition of IL 2 to cultures that did not respond to antigen had no effect. Antigen-responsive cultures contained endogenous IL 2 as well, and the antigen-induced lymphocyte proliferation was correlated with IL 2 production. However, the results suggested that IL 2 production by the patients' T cells was insufficient or actively shut off, and that this was responsible for the premature cessation of their DNA synthesis. Supernatants from 60% of the T cell cultures treated with malaria antigen and from 30% treated with RBC ghost antigen contained interferon-gamma (IFN-gamma), as determined by a cytopathic effect inhibition assay combined with acid treatment and antibody neutralization or by an IFN-gamma-specific ELISA. There was no obvious correlation between antigen-induced lymphocyte proliferation and the presence of IFN-gamma in the culture supernatants. A high IFN-gamma activity was also seen in antigen-treated cultures from P. falciparum-immune donors living in highly endemic malaria areas. In contrast, no IFN-gamma was found in supernatants of antigen-treated T cells from healthy donors or patients with Plasmodium vivax malaria. Thus, the IFN-gamma activity of these cultures appears to reflect the presence of antigen-reactive T cells and may be useful as a sensitive indicator of cellular immunity in P. falciparum malaria.
急性感染疟疾患者的T细胞在体外对恶性疟原虫抗原产生反应时，表现出与疾病相关的DNA合成刺激。这种反应微弱且短暂，提示有抑制机制的诱导。添加到抗原刺激的T细胞培养物中的外源性T细胞生长因子（IL-2）增强了对抗原反应性培养物中的增殖，表明淋巴细胞表达了IL-2受体。相比之下，将IL-2添加到对抗原无反应的培养物中则没有效果。对抗原反应的培养物也含有内源性IL-2，并且抗原诱导的淋巴细胞增殖与IL-2产生相关。然而，结果表明患者T细胞产生的IL-2不足或被主动关闭，这导致了它们DNA合成的过早停止。通过细胞病变效应抑制试验结合酸处理和抗体中和或通过IFN-γ特异性ELISA测定，60%用疟疾抗原处理的T细胞培养物上清液和30%用红细胞膜抗原处理的培养物上清液中含有干扰素-γ（IFN-γ）。抗原诱导的淋巴细胞增殖与培养物上清液中IFN-γ的存在之间没有明显的相关性。在生活在疟疾高度流行地区的恶性疟原虫免疫供体的抗原处理培养物中也观察到高IFN-γ活性。相比之下，在健康供体或间日疟患者的抗原处理T细胞上清液中未发现IFN-γ。因此，这些培养物的IFN-γ活性似乎反映了抗原反应性T细胞的存在，并且可能作为恶性疟原虫疟疾中细胞免疫的敏感指标。
