Laboratory of Mycobacterial Diseases and Cellular Immunology, Division of Bacterial, Parasitic, and Allergenic Products, CBER/FDA, HFM 431, Rockville, MD 20852, USA.
Microbes Infect. 2010 Jan;12(1):28-36. doi: 10.1016/j.micinf.2009.09.012. Epub 2009 Sep 23.
Although survival of primary infection with the live vaccine strain (LVS) of Francisella tularensis depends on interferon gamma (IFN-gamma), the relative importance of IFN-gamma to secondary protective immunity in vivo has not been clearly established. Here we examine the role of IFN-gamma in T cell priming and expression of vaccine-induced protection against lethal intraperitoneal challenge of mice. Large amounts of IFN-gamma were detected between days 3 and 7 in the sera of LVS-immunized mice, while relatively small amounts were found transiently after secondary LVS challenge. Consistent with the production of this cytokine, mice lacking IFN-gamma (gamma interferon knockout, GKO, mice) could not be successfully vaccinated with LVS or an attenuated mglA mutant of F. novicida to withstand secondary Francisella LVS challenge. Further, splenocytes from such primed mice did not adoptively transfer protection to naive GKO recipient mice in vivo, nor control the intramacrophage growth of LVS in vitro. Finally, LVS-immune WT mice depleted of IFN-gamma prior to intraperitoneal challenge survived only the lowest doses of challenge. Thus successful priming of protective LVS-immune T cells, as well as complete expression of protection against Francisella during secondary challenge, depends heavily on IFN-gamma.
尽管原发性感染土拉弗朗西斯菌活疫苗株（LVS）的存活依赖于干扰素γ（IFN-γ），但 IFN-γ 对体内二次保护免疫的相对重要性尚未明确确定。在这里，我们研究了 IFN-γ 在 T 细胞启动和疫苗诱导的保护作用中的作用，以抵抗致命的腹腔内弗朗西斯菌 LVS 挑战。LVS 免疫小鼠的血清中在第 3 天至第 7 天检测到大量 IFN-γ，而在二次 LVS 挑战后则短暂地发现了相对少量的 IFN-γ。与这种细胞因子的产生一致，缺乏 IFN-γ（γ干扰素敲除，GKO 小鼠）的小鼠不能成功接种 LVS 或减毒 mglA 突变的弗氏新诺卡氏菌，以抵御二次弗朗西斯菌 LVS 挑战。此外，来自这些致敏小鼠的脾细胞不能在体内将保护作用传递给幼稚的 GKO 受体小鼠，也不能控制 LVS 在体外的巨噬细胞内生长。最后，在腹腔内挑战之前，LVS 免疫的 WT 小鼠耗尽 IFN-γ 后，仅能存活最低剂量的挑战。因此，保护性 LVS 免疫 T 细胞的成功启动，以及在二次挑战期间对弗朗西斯菌的完全保护作用，严重依赖于 IFN-γ。
