Reduced primary antigen‐specific T‐cell precursor frequencies in neonates is associated with deficient interleukin‐2 production
Reduced primary antigen‐specific T‐cell precursor frequencies in neonates is associated with deficient interleukin‐2 production
复制标题
新生儿初级抗原特异性 T 细胞前体频率降低与白细胞介素 2 生成不足相关
作者：
J. Hassan;D. Reen
临床证据表明，与患有相同原发感染的成人相比，新生儿对原发感染的细胞免疫反应延迟。调节新生儿抗原特异性T细胞免疫发育的机制尚不清楚。我们在体外检测了成人和新生儿对非召回抗原锁孔帽状血蓝蛋白(KLH)的初步免疫反应。我们在此报告，传统的批量培养方法显示新生儿的增殖反应减少，尽管没有达到统计学意义。使用有限稀释分析，新生儿的KLH特异性T淋巴细胞的频率比成人低10-100倍。与成人相比，KLH刺激的新生儿单个核细胞(MNC)上清液中IL-2的产生显著降低。在成人和新生儿培养中，外源IL-2的加入使前体频率增加了两倍。与IL-2的分泌水平相比，在抗原刺激的新生儿MNC中，IL-2mRNA的表达更高，尽管其增殖程度较低。这些观察表明，新生儿和成人对主要抗原挑战的体外反应性不同。由于在细胞裂解物中未检测到IL-2，IL-2mRNA的高水平和IL-2的低产生提示新生儿MNC不能翻译IL-2。这种IL-2产生的不足可能解释了前体频率降低的原因，提示未能招募T淋巴细胞来扩大KLH特异性T细胞的应答。这些观察对于了解新生儿初级免疫反应的发展和免疫成熟具有重要意义。
Clinical evidence has indicated that the neonatal cell‐mediated immune response to primary infection is delayed when compared to that of adults with the same primary infection. The mechanisms regulating the development of antigen‐specific T‐cell immunity in neonates remain to be elucidated. We examined the primary immune response to the non‐recall antigen, keyhole limpet haemocyanin (KLH) in adults and neonates in vitro. We report here that conventional bulk culture methods show reduced proliferative responses in neonates although statistical significance was not achieved. Using limiting dilution analysis, the frequencies of KLH‐specific T lymphocytes were 10–100‐fold lower in neonates when compared to adults. Interleukin‐2 (IL‐2) production was significantly lower in the supernatants of neonatal mononuclear cells (MNC) stimulated with KLH when compared to adults. Addition of exogenous IL‐2 increased precursor frequencies twofold in both adult and newborn cultures. In contrast to the secreted IL‐2 levels, IL‐2 mRNA expression was higher in antigen‐stimulated neonatal MNC preparations, even though proliferation was lower. These observations indicate differential in vitro responsiveness in neonates and adults to primary antigenic challenge. Since no IL‐2 was detected in cell lysates, the presence of high levels of IL‐2 mRNA and low IL‐2 production suggests inability by neonatal MNC to translate IL‐2. This deficiency in IL‐2 production may explain the reduced precursor frequencies, suggesting failure to recruit T lymphocytes in order to expand the KLH‐specific T‐cell response. These observations are important for the understanding of the development of primary immune responses and immunological maturation in neonates.
DOI：
10.1172/jci115029
发表时间：
1991
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Splawski,JB;Jelinek,DF;Lipsky,PE
通讯作者：
Lipsky,PE