The generation of th memory in neonates versus adults: Prolonged primary Th2 effector function and impaired development of Th1 memory effector function in murine neonates
The generation of th memory in neonates versus adults: Prolonged primary Th2 effector function and impaired development of Th1 memory effector function in murine neonates
复制标题
DOI：
10.4049/jimmunol.166.2.918
复制
发表时间：
2001-01-15
影响因子：
4.4
通讯作者：
Guevara, P
中科院分区：
文献类型：
--
作者：
Adkins, P;Bu, YR;Guevara, P
新生儿期的免疫接种往往会导致Th2偏向的继发性反应。为了了解这一现象的调节，我们研究了Th发育的所有阶段，从初级效应器的产生到初级效应器阶段的持续时间，再到记忆效应器功能的产生。首先，我们以前报道过，虽然新生儿淋巴结中的主要反应是成熟的、混合的Th1/Th2样反应，但同一动物的脾中的主要反应完全是Th2样反应。为了确定Th2显性二次反应是否是由于脾中Th2极化的主要功能，新生儿在免疫前进行了脾切除。即使在没有原发新生儿脾反应的情况下，新生儿的继发反应也是以Th2为主。因此，新生儿脾中以Th2为主的初级反应不需要在淋巴结中产生以Th2为主的记忆。其次，我们比较了新生儿和成人的主要反应期的动力学。在成人中，淋巴结和脾中的抗原特异性Th2功能迅速消失，相反，初级Th2功能在两个新生儿器官中持续到5wk。第三，在最初免疫的新生动物和成年动物中检测了Th记忆反应的产生，这些实验表明，新生儿在Th1记忆效应功能的发育过程中受到选择性的损害。总而言之，这些结果表明，新生儿在免疫反应的所有阶段都偏向Th2功能。
Immunization during the neonatal period often results in Th2-biased secondary responses. To understand the regulation of this phenomenon, we have examined all phases of Th development, from the generation of primary effecters to the duration of the primary effector stage to the production of memory effector function. First, we had previously reported that although primary responses in the neonatal lymph nodes are mature, mixed Th1/Th2-like, primary responses in the spleens of the same animals are exclusively Th2-like. To determine whether Th2-dominant secondary responses are due to the Th2-polarized primary function in the spleen, neonates were splenectomized before immunization. Even in the absence of primary neonatal splenic responses, the secondary responses of neonates were Th2 dominant. Thus, the overwhelmingly Th2 primary responses in the neonatal spleen are not required to generate Th2-dominant memory in the lymph nodes. Second, we have compared the kinetics of the primary response phase in neonates and adults. In adults, Ag-specific Th2 function disappeared rapidly from both the lymph nodes and spleen, In contrast, primary Th2 function persisted out to 5 wk in both neonatal organs. Third, the generation of Th memory responses was examined in animals initially immunized as neonates and in adults, These experiments demonstrated that neonates are selectively impaired in the development of Th1 memory effector function. Together, these results indicate that neonates are biased to Th2 function at all phases of an immune response.