Thom M L, Hope J C, McAulay M, Villarreal-Ramos B, Coffey T J, Stephens S, Vordermeier H M, Howard C J
Institute for Animal Health, Compton, Newbury, Berkshire RG20 7NN, UK.
Vet Immunol Immunopathol. 2006 Nov 15;114(1-2):25-36. doi: 10.1016/j.vetimm.2006.07.001. Epub 2006 Aug 14.
Protection against tuberculosis (TB) is associated with Th1-type cell-mediated immunity (CMI). Whilst the intradermal injection of partially purified derivatives of tuberculin (PPD) represents the classic test assessing the delayed type hypersensitivity (DTH) response used in both humans and cattle for diagnosing TB, it has been suggested that the test may modulate host CMI responses. To investigate the kinetics of the development of the DTH response and its subsequent effect on CMI responses, groups of 6-month old calves were inoculated intranasally with 8 x 10(4) cfu of Mycobacterium bovis, subjected to the comparative intradermal tuberculin test (TT) using bovine and avian PPD (PPD-B, PPD-A) at various time intervals post-infection, and immune responses compared. These included DTH, lymphocyte proliferation, IgG production, and synthesis of the cytokines: IFNgamma, IL-10, IL-4, IL-6, and IL-13. All animals were subjected to post-mortem examination. The kinetics of the development of the DTH response assessed in the TT was such that infected cattle could be identified as early as 3 weeks post-infection, which correlated with the detection of an antigen-specific IFNgamma response. Transient increases in plasma-derived IFNgamma as a result of TT during an established TB infection were more pronounced when blood was stimulated with PPD-A compared with PPD-B stimulation. This has the potential to mask diagnosis of infection as a result of the stronger avian-bias if the IFNgamma test is used the week following TT. Disease pathology was not affected by TT. A transient failure to a second TT was observed in 1 of 30 animals and the time (post-infection) at which the TT is administered may be of significance. In serum, IgG responses to PPD-B, which were undetectable prior to TT, were elevated after TT and were most pronounced in cattle that were TT at 6 weeks post-infection. Other cytokines were also affected by the TT; IL-4 mRNA levels increased and IL-6 mRNA levels decreased, whilst PPD-B specific IL-10 protein synthesis was enhanced. These observations may offer the potential for further diagnostic assays that could complement the TT and IFNgamma test.
对结核病（TB）的保护与Th1型细胞介导的免疫（CMI）相关。虽然皮内注射结核菌素的部分纯化衍生物（PPD）是评估用于人类和牛结核病诊断的迟发型超敏反应（DTH）的经典试验，但有人认为该试验可能会调节宿主的CMI反应。为了研究DTH反应的发展动力学及其对CMI反应的后续影响，将6月龄犊牛分组，在感染后不同时间间隔经鼻接种8×10⁴cfu牛分枝杆菌，使用牛和禽PPD（PPD - B、PPD - A）进行比较皮内结核菌素试验（TT），并比较免疫反应。这些反应包括DTH、淋巴细胞增殖、IgG产生以及细胞因子：IFNγ、IL - 10、IL - 4、IL - 6和IL - 13的合成。所有动物均进行尸检。在TT中评估的DTH反应的发展动力学表明，感染牛最早可在感染后3周被识别，这与抗原特异性IFNγ反应的检测相关。与用PPD - B刺激相比，在用PPD - A刺激血液时，在已确诊的结核病感染期间，由于TT导致血浆来源的IFNγ短暂增加更为明显。如果在TT后一周使用IFNγ试验，由于更强的禽类偏向性，这有可能掩盖感染的诊断。疾病病理学不受TT影响。在30只动物中有1只观察到对第二次TT出现短暂无反应，并且TT给药的时间（感染后）可能具有重要意义。在血清中，对PPD - B的IgG反应在TT之前无法检测到，在TT后升高，并且在感染后6周进行TT的牛中最为明显。其他细胞因子也受TT影响；IL - 4 mRNA水平升高，IL - 6 mRNA水平降低，而PPD - B特异性IL - 10蛋白合成增强。这些观察结果可能为进一步的诊断检测提供潜力，这些检测可以补充TT和IFNγ试验。
