Nguyen Q H, Roberts R L, Ank B J, Lin S J, Lau C K, Stiehm E R
Department of Pediatrics, Children's Hospital, University of California at Los Angeles, 90095, USA.
Clin Diagn Lab Immunol. 1998 Jan;5(1):98-104. doi: 10.1128/CDLI.5.1.98-104.1998.
Newborn infants are more susceptible to infections due in part to deficiencies in the cytotoxic functions of their lymphocytes. We investigated the ability of interleukin-2 (IL-2) and IL-12 to enhance the cytotoxicity of neonatal (cord blood) and adult mononuclear cells (MNCs) in both natural killer (NK) cell and antibody-dependent cellular cytotoxicity (ADCC) assays. The cytotoxic activity of cord blood MNCs was less than 50% that of adult MNCs in most assays prior to exposure to cytokines. Incubation with IL-2 (100 U/ml) or IL-12 (1 ng/ml) for 18 h increased the NK cell activity (using K562 target cells) of both cord blood and adult MNCs, and the combination of IL-2 and IL-12 increased cord blood cytotoxicity threefold, making the cytotoxicity of cord blood cells equivalent to that of adult cells treated with the same cytokines. In ADCC assays with chicken erythrocyte targets, the combination of IL-2 and IL-12 increased the cytotoxicities of both cord blood and adult MNCs, with greater enhancement again seen with cord blood cells. In assays with NK cell-resistant CEM cells coated with human immunodeficiency virus (HV) gp120 antigen in the presence of hyperimmune anti-HIV immunoglobulin, ADCC of cord blood MNCs was about 50% that of adult MNCs; ADCC of cord blood MNCs increased two- to threefold with the addition of IL-2 and IL-12, whereas ADCC of adult MNCs did not increase. Incubation of cord blood cells, but not adult cells, with IL-2 or IL-12 for 1 week increased the percentage of CD16+/CD56+ cells two- to fivefold and enhanced ADCC activity. Thus, IL-2 and IL-12 greatly enhance both the NK cell and ADCC activities of neonatal MNCs and increase the number of NK cells in longer-term culture.
新生儿更容易受到感染，部分原因是其淋巴细胞的细胞毒性功能存在缺陷。我们在自然杀伤（NK）细胞和抗体依赖性细胞毒性（ADCC）试验中，研究了白细胞介素-2（IL-2）和IL-12增强新生儿（脐血）和成人单核细胞（MNCs）细胞毒性的能力。在暴露于细胞因子之前，在大多数试验中，脐血MNCs的细胞毒性活性不到成人MNCs的50%。用IL-2（100 U/ml）或IL-12（1 ng/ml）孵育18小时可增加脐血和成人MNCs的NK细胞活性（使用K562靶细胞），IL-2和IL-12联合使用可使脐血细胞毒性增加三倍，使脐血细胞的细胞毒性与用相同细胞因子处理的成人细胞相当。在用鸡红细胞靶标的ADCC试验中，IL-2和IL-12联合使用可增加脐血和成人MNCs的细胞毒性，脐血细胞的增强作用再次更明显。在存在超免疫抗HIV免疫球蛋白的情况下，用人类免疫缺陷病毒（HV）gp120抗原包被的NK细胞抗性CEM细胞进行的试验中，脐血MNCs的ADCC约为成人MNCs的50%；添加IL-2和IL-12后，脐血MNCs的ADCC增加了两到三倍，而成人MNCs的ADCC没有增加。用IL-2或IL-12孵育脐血细胞1周可使CD16+/CD56+细胞百分比增加两到五倍，并增强ADCC活性，但对成人细胞无效。因此，IL-2和IL-12可极大地增强新生儿MNCs的NK细胞和ADCC活性，并在长期培养中增加NK细胞数量。
