Haque Ashraful, Easton Anna, Smith Debbie, O'Garra Anne, Van Rooijen Nico, Lertmemongkolchai Ganjana, Titball Richard W, Bancroft Gregory J
Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, UK.
J Infect Dis. 2006 Feb 1;193(3):370-9. doi: 10.1086/498983. Epub 2005 Dec 27.
Antigen-specific T cells are important sources of interferon (IFN)-gamma for acquired immunity to intracellular pathogens, but they can also produce IFN- gamma directly via a "bystander" activation pathway in response to proinflammatory cytokines. We investigated the in vivo role of cytokine- versus antigen-mediated T cell activation in resistance to the pathogenic bacterium Burkholderia pseudomallei. IFN-gamma, interleukin (IL)-12, and IL-18 were essential for initial bacterial control in infected mice. B. pseudomallei infection rapidly generated a potent IFN-gamma response from natural killer (NK) cells, NK T cells, conventional T cells, and other cell types within 16 h after infection, in an IL-12- and IL-18-dependent manner. However, early T cell- and NK cell-derived IFN-gamma responses were functionally redundant in cell depletion studies, with IFN-gamma produced by other cell types, such as major histocompatibility complex class II(int) F4/80(+) macrophages being sufficient for initial resistance. In contrast, B. pseudomallei-specific CD4(+) T cells played an important role during the later stage of infection. Thus, the T cell response to primary B. pseudomallei infection is biphasic, an early cytokine-induced phase in which T cells appear to be functionally redundant for initial bacterial clearance, followed by a later antigen-induced phase in which B. pseudomallei-specific T cells, in particular CD4(+) T cells, are important for host resistance.
抗原特异性T细胞是获得性细胞内病原体免疫中干扰素（IFN）-γ的重要来源，但它们也可通过“旁观者”激活途径直接产生IFN-γ，以响应促炎细胞因子。我们研究了细胞因子介导与抗原介导的T细胞激活在抵抗致病性细菌伯克霍尔德菌感染中的体内作用。IFN-γ、白细胞介素（IL）-12和IL-18对于感染小鼠的初始细菌控制至关重要。伯克霍尔德菌感染在感染后16小时内迅速从自然杀伤（NK）细胞、NK T细胞、传统T细胞和其他细胞类型中产生强大的IFN-γ反应，且该反应依赖于IL-12和IL-18。然而，在细胞耗竭研究中，早期T细胞和NK细胞来源的IFN-γ反应在功能上是冗余的，其他细胞类型产生的IFN-γ，如主要组织相容性复合体II类（int）F4/80（+）巨噬细胞产生的IFN-γ足以实现初始抵抗。相比之下，伯克霍尔德菌特异性CD4（+）T细胞在感染后期发挥重要作用。因此，T细胞对原发性伯克霍尔德菌感染的反应是双相的，早期是细胞因子诱导阶段，在此阶段T细胞在初始细菌清除方面似乎功能冗余，随后是后期抗原诱导阶段，在此阶段伯克霍尔德菌特异性T细胞，特别是CD4（+）T细胞，对宿主抵抗至关重要。
