Allen A J, Stabel J R, Robbe-Austerman S, Park K T, Palmer M V, Barrington G M, Lahmers K K, Hamilton Mary Jo, Davis William C
Department of Veterinary Clinical Sciences, Washington State University, Pullman, WA 99164-7060, USA.
Vet Immunol Immunopathol. 2012 Oct 15;149(3-4):286-91. doi: 10.1016/j.vetimm.2012.07.010. Epub 2012 Jul 27.
A calf model was used to determine if the depletion of CD4 T cells prior to inoculation of Mycobacterium avium subsp. paratuberculosis (Map) would delay development of an immune response to Map and accelerate disease progression. Ileal cannulas were surgically implanted in 5 bull calves at 2 months of age. Two calves were depleted of CD4 T cells by intravenous injection of anti-bovine CD4 antibody administered 24h prior to inoculation with Map. The two CD4-depleted calves and one non-depleted calf were inoculated via ileal cannula with 1 × 10(8)cfu live Map every 3 days for a total of 4 inoculations. Two additional calves served as non-depleted and uninfected controls. Injection with the anti-CD4 mAb reduced the frequency of CD4 T cells from a pre-depletion average of 15% to less than 1% in PBMC at 24h. However, a consistent proliferative response dominated by CD4 T cells, developed in both treated and untreated calves over the course of the 6-month study period. Recovery of Map from serial biopsies obtained from the CD4-depleted and non-depleted calves after Map infection did not differ. In addition, CD4 depletion did not increase the level of Map shed in the feces over the non-depleted animal.
使用犊牛模型来确定在接种副结核分枝杆菌（Map）之前耗尽CD4 T细胞是否会延迟对Map的免疫反应发展并加速疾病进展。在5头2月龄的公牛犊中通过手术植入回肠插管。在接种Map前24小时，通过静脉注射抗牛CD4抗体使2头犊牛的CD4 T细胞耗尽。对2头CD4细胞耗尽的犊牛和1头未耗尽的犊牛每隔3天通过回肠插管接种1×10(8)cfu活Map，共接种4次。另外2头犊牛作为未耗尽且未感染的对照。注射抗CD4单克隆抗体使24小时时外周血单核细胞中CD4 T细胞的频率从耗尽前的平均15%降低至不到1%。然而，在6个月的研究期间，在经过处理和未处理的犊牛中均出现了以CD4 T细胞为主导的一致增殖反应。Map感染后，从CD4细胞耗尽和未耗尽的犊牛获得的系列活检组织中Map的回收率没有差异。此外，与未耗尽的动物相比，耗尽CD4并没有增加粪便中排出的Map水平。
