Pakpour Nazzy, Zaph Colby, Scott Phillip
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
J Immunol. 2008 Jun 15;180(12):8299-305. doi: 10.4049/jimmunol.180.12.8299.
Central memory CD4(+) T cells provide a pool of lymph node-homing, Ag-experienced cells that are capable of responding rapidly after a secondary infection. We have previously described a population of central memory CD4(+) T cells in Leishmania major-infected mice that were capable of mediating immunity to a secondary infection. In this study, we show that the Leishmania-specific central memory CD4(+) T cells require IL-12 to produce IFN-gamma, demonstrating that this population needs additional signals to develop into Th1 cells. In contrast, effector cells isolated from immune mice produced IFN-gamma in vitro or in vivo in the absence of IL-12. In addition, we found that when central memory CD4(+) T cells were adoptively transferred into IL-12-deficient hosts, many of the cells became IL-4 producers. These studies indicate that the central memory CD4(+) T cell population generated during L. major infection is capable of developing into either Th1 or Th2 effectors. Thus, continued IL-12 production may be required to ensure the development of Th1 cells from this central memory T cell pool, a finding that has direct relevance to the design of vaccines dependent upon central memory CD4(+) T cells.
中枢记忆性CD4(+) T细胞提供了一群归巢至淋巴结、具有抗原接触经验的细胞，这些细胞在再次感染后能够迅速做出反应。我们之前曾描述过在感染硕大利什曼原虫的小鼠体内存在一群中枢记忆性CD4(+) T细胞，它们能够介导对再次感染的免疫。在本研究中，我们发现利什曼原虫特异性中枢记忆性CD4(+) T细胞需要IL-12来产生IFN-γ，这表明这群细胞需要额外的信号才能发育为Th1细胞。相比之下，从免疫小鼠中分离出的效应细胞在体外或体内无IL-12的情况下也能产生IFN-γ。此外，我们发现当中枢记忆性CD4(+) T细胞被过继转移至IL-12缺陷宿主时，许多细胞会变成IL-4产生细胞。这些研究表明，在硕大利什曼原虫感染期间产生的中枢记忆性CD4(+) T细胞群体能够发育为Th1或Th2效应细胞。因此，可能需要持续产生IL-12以确保从这个中枢记忆性T细胞库中发育出Th1细胞，这一发现与依赖中枢记忆性CD4(+) T细胞的疫苗设计直接相关。
