Pais T F, Silva R A, Smedegaard B, Appelberg R, Andersen P
Department of TB Immunology, Statens Serum Institut, Copenhagen, Denmark.
Immunology. 1998 Sep;95(1):69-75. doi: 10.1046/j.1365-2567.1998.00561.x.
The delayed-type hypersensitivity (DTH) to purified protein derivative (PPD) test has been used to infer about protective immunity to Mycobacterium tuberculosis and to diagnose tuberculosis. We showed that in memory tuberculosis-immune mice both DTH to PPD and resistance to M. tuberculosis could be effectively elicited in the footpad and both reactions led to the accumulation of reactive T cells in the regional lymph nodes with a CD4+ phenotype and characterized by the secretion of high levels of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) and no IL-4. By adoptive transfer into nude mice of highly purified CD4+ T cells harvested during the recall of protective immunity it was confirmed that this population mediated both manifestations. However, the specificity of the T cells recruited during these processes were found to differ markedly; T cells involved in protection to a challenge with live tuberculosis bacilli recognized predominantly low-mass culture filtrate antigens below 15 000 MW, while cells recruited during DTH to PPD were directed to molecular mass fractions between 15 000 and 31 000. Using single purified antigens we showed that the latter cells recognized the secreted mycobacterial protein Ag85B and the heat-shock proteins, DnaK and GroEL. Protective T cells, in contrast, were characterized by a very high frequency of T cells directed to the ESAT-6 peptide 1-20.
对纯化蛋白衍生物（PPD）试验的迟发型超敏反应（DTH）已被用于推断对结核分枝杆菌的保护性免疫并诊断结核病。我们发现，在记忆性结核免疫小鼠中，足垫内可有效引发对PPD的DTH和对结核分枝杆菌的抵抗力，两种反应均导致具有CD4 +表型的反应性T细胞在局部淋巴结中积聚，其特征是分泌高水平的白细胞介素-2（IL-2）和干扰素-γ（IFN-γ），且无IL-4。通过将在保护性免疫回忆期间收获的高度纯化的CD4 + T细胞过继转移到裸鼠中，证实了这群细胞介导了两种表现。然而，发现在这些过程中募集的T细胞的特异性明显不同；参与抵抗活结核杆菌攻击的T细胞主要识别分子量低于15000 MW的低质量培养滤液抗原，而在对PPD的DTH过程中募集的细胞则针对分子量在15000至31000之间的组分。使用单一纯化抗原，我们发现后者细胞识别分泌的分枝杆菌蛋白Ag85B和热休克蛋白DnaK及GroEL。相比之下，保护性T细胞的特征是针对ESAT-6肽1-20的T细胞频率非常高。
