Lertmemongkolchai G, Cai G, Hunter C A, Bancroft G J
Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
J Immunol. 2001 Jan 15;166(2):1097-105. doi: 10.4049/jimmunol.166.2.1097.
The bacterium Burkholderia pseudomallei causes a life-threatening disease called melioidosis. In vivo experiments in mice have identified that a rapid IFN-gamma response is essential for host survival. To identify the cellular sources of IFN-gamma, spleen cells from uninfected mice were stimulated with B. pseudomallei in vitro and assayed by ELISA and flow cytometry. Costaining for intracellular IFN-gamma vs cell surface markers demonstrated that NK cells and, more surprisingly, CD8(+) T cells were the dominant sources of IFN-gamma. IFN-gamma(+) NK cells were detectable after 5 h and IFN-gamma(+) CD8(+) T cells within 15 h after addition of bacteria. IFN-gamma production by both cell populations was inhibited by coincubation with neutralizing mAb to IL-12 or IL-18, while a mAb to TNF had much less effect. Three-color flow cytometry showed that IFN-gamma-producing CD8(+) T cells were of the CD44(high) phenotype. The preferential activation of NK cells and CD8(+) T cells, rather than CD4(+) T cells, was also observed in response to Listeria monocytogenes or a combination of IL-12 and IL-18 both in vitro and in vivo. This rapid mechanism of CD8(+) T cell activation may be an important component of innate immunity to intracellular pathogens.
类鼻疽伯克霍尔德菌可引发一种名为类鼻疽的危及生命的疾病。小鼠体内实验已证实，快速的γ干扰素反应对宿主存活至关重要。为确定γ干扰素的细胞来源，用类鼻疽伯克霍尔德菌体外刺激未感染小鼠的脾细胞，并通过酶联免疫吸附测定法（ELISA）和流式细胞术进行检测。细胞内γ干扰素与细胞表面标志物的共染色显示，自然杀伤细胞（NK细胞），更令人惊讶的是，CD8(+) T细胞是γ干扰素的主要来源。添加细菌后5小时可检测到γ干扰素(+) NK细胞，15小时内可检测到γ干扰素(+) CD8(+) T细胞。与抗白细胞介素12（IL-12）或抗白细胞介素18（IL-18）的中和单克隆抗体共同孵育可抑制这两种细胞群体产生γ干扰素，而抗肿瘤坏死因子（TNF）单克隆抗体的作用则小得多。三色流式细胞术显示，产生γ干扰素的CD8(+) T细胞具有CD44(高)表型。在体外和体内，对单核细胞增生李斯特菌或IL-12与IL-18的组合作出反应时，也观察到NK细胞和CD8(+) T细胞而非CD4(+) T细胞的优先激活。CD8(+) T细胞的这种快速激活机制可能是针对细胞内病原体的固有免疫的重要组成部分。
