Kohl S
Department of Pediatrics, University of California Medical School, San Francisco General Hospital 94110.
J Immunol. 1990 Jan 1;144(1):307-12.
One-week-old mice were protected against a uniformly lethal herpes simplex virus (HSV) infection by IL-2 alone, but especially by the addition of human mononuclear cells (MC) plus IL-2. The dose response of IL-2 was biphasic. The addition of MC from cord blood did not enhance IL-2-mediated survival. Because the effect of IL-2 alone, or IL-2 plus MC, was ablated by anti-IFN-gamma and human neonates have an IFN-gamma production defect, the protective effect of MC plus human IFN-gamma (HuIFN-gamma) was tested. MC from adults cultured for 5 days in HuIFN-gamma afforded protection. At least 1 x 10(6) HuIFN-gamma-treated MC were required with increasing survival to 1 x 10(7) MC. The effector cell activity was ablated by adherence, silica, L-leucine methyl ester treatment or treatment with Leu-M3 plus C (all macrophage markers), and OKT4 plus C treatment (CD4 marker). Use of Leu-11, Leu-7, OKT3, or OKT8 plus C did not inhibit protection and excluded NK or T cell participation. In addition to survival, the ability to produce anti-HSV antibody was reconstituted. For the first time protection was afforded by human cord blood MC after treatment with HuIFN in vitro. We have identified an IFN-gamma-driven protection system against murine neonatal HSV infection mediated by human adult- or cord blood-derived CD4-positive macrophages. Protection is associated with enhanced effector cell function and reconstitution of the neonatal antibody production defect.
仅白细胞介素-2（IL-2）就能保护一周大的小鼠免受单纯疱疹病毒（HSV）的致命性感染，而添加人单核细胞（MC）加IL-2时保护效果更佳。IL-2的剂量反应呈双相性。添加脐血中的MC并不能增强IL-2介导的存活率。由于抗干扰素-γ（IFN-γ）可消除单独使用IL-2或IL-2加MC的效果，且人类新生儿存在IFN-γ产生缺陷，因此测试了MC加人IFN-γ（HuIFN-γ）的保护作用。在HuIFN-γ中培养5天的成人MC具有保护作用。至少需要1×10⁶经HuIFN-γ处理的MC，随着MC数量增加到1×10⁷，存活率也会提高。效应细胞活性可通过贴壁、二氧化硅、L-亮氨酸甲酯处理或用Leu-M3加C（所有巨噬细胞标志物）以及OKT4加C处理（CD4标志物）来消除。使用Leu-11、Leu-7、OKT3或OKT8加C不会抑制保护作用，排除了自然杀伤细胞（NK）或T细胞的参与。除了提高存活率外，还恢复了产生抗HSV抗体的能力。首次在体外经HuIFN处理后，人脐血MC具有保护作用。我们已经确定了一种由IFN-γ驱动的针对小鼠新生儿HSV感染的保护系统，该系统由人成人或脐血来源的CD4阳性巨噬细胞介导。保护作用与效应细胞功能增强和新生儿抗体产生缺陷的恢复有关。
