Shibuya K, Robinson D, Zonin F, Hartley S B, Macatonia S E, Somoza C, Hunter C A, Murphy K M, O'Garra A
Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Inc., Palo Alto, CA 94303, USA.
J Immunol. 1998 Feb 15;160(4):1708-16.
The development of Th1- or Th2-type responses determines the type of immune response that is elicited in response to Ag. Responsiveness to IL-12 is critical for the development of Th1-type CD4+ T cells required for cell-mediated immune responses. Addition of IL-12 to primary cultures of CD4+ T cells stimulated with OVA and splenocytes or dendritic cells resulted in the development of a Th1 phenotype with the capacity to secrete high levels of IFN-gamma upon restimulation with splenic APC. The present study shows that using dendritic cells to present Ag upon restimulation reveals a requirement for additional cofactors, including IL-1 alpha and TNF-alpha, which were provided by spleen cells but not dendritic cells. Furthermore, these cofactors are required for optimal IL-12-induced Th1 development in BALB/c but not C57BL/6 mice. This differential requirement for such cofactors in IL-12-driven Th1 development may play a role in genetic predisposition to Th1 or Th2 responses to infectious agents.
Th1型或Th2型应答的发展决定了针对抗原所引发的免疫应答类型。对白细胞介素-12（IL-12）的反应性对于细胞介导免疫应答所需的Th1型CD4 + T细胞的发育至关重要。将IL-12添加到用卵清蛋白（OVA）以及脾细胞或树突状细胞刺激的CD4 + T细胞原代培养物中，会导致Th1表型的发展，该表型在受到脾抗原呈递细胞（APC）再次刺激时能够分泌高水平的γ干扰素（IFN-γ）。本研究表明，在再次刺激时使用树突状细胞呈递抗原揭示了对其他辅助因子的需求，包括IL-1α和肿瘤坏死因子-α（TNF-α），这些因子由脾细胞而非树突状细胞提供。此外，在BALB / c小鼠而非C57BL / 6小鼠中，这些辅助因子是IL-12诱导的Th1发育所必需的。在IL-12驱动的Th1发育中对这类辅助因子的这种差异需求可能在对感染因子的Th1或Th2应答的遗传易感性中起作用。
