Kondratieva T K, Kobets N V, Khaidukov S V, Yeremeev V V, Lyadova I V, Apt A S, Tam M F, Stevenson M M
Experimental Immunogenetics Laboratory, Central Institute for Tuberculous and Laboratory for Immunochemistry, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
Clin Exp Immunol. 2000 Aug;121(2):275-82. doi: 10.1046/j.1365-2249.2000.01222.x.
Pseudomonas aeruginosa-resistant BALB/c and susceptible C57Bl/6 (B6) mice were immunized with heat-killed Pseudomonas either in the foot pad or via the trachea, and panels of Pseudomonas-specific T cell clones were developed from lymph nodes and lungs. All clones from either strain, whether of lymph node or lung origin, were CD3+CD4+CD8-TCRalphabeta+. The efficacy of cloning from lymph node cells was comparable between BALB/c and B6 mice. All lymph node BALB/c clones proliferated in response to Pseudomonas antigen in a dose-dependent manner, and this response was MHC class II-restricted. Vigorous proliferation by a considerable proportion of B6 T cell clones occurred in the absence of specific antigen. Lymph node clones from either strain could be categorized as either Th1 or Th0 on the basis of interferon-gamma (IFN-gamma)/IL-4 production. In either mouse strain the efficacy of cloning from lung tissue was substantially lower than from lymph nodes, but the efficacy of cloning from BALB/c compared with B6 lungs was higher. Four lung T cell clones from BALB/c and two from B6 mice were expanded for further analyses, and an interstrain difference was observed in cytokine production. Both B6 lung T cell clones were Th1-like and produced IFN-gamma but not IL-4 and IL-10, whereas four BALB/c lung T cell clones were Th2-like and produced IL-4 and IL-10 but not IFN-gamma. These observations suggest that differences in the CD4+ Th response in the lung may contribute to differences among inbred mouse strains in the level of resistance to bronchopulmonary Pseudomonas infection.
用热灭活的铜绿假单胞菌分别经足垫或气管免疫对铜绿假单胞菌耐药的BALB/c小鼠和敏感的C57Bl/6(B6)小鼠,然后从淋巴结和肺中培养出铜绿假单胞菌特异性T细胞克隆。来自这两种品系的所有克隆,无论来源于淋巴结还是肺,均为CD3+CD4+CD8-TCRαβ+。BALB/c小鼠和B6小鼠从淋巴结细胞中克隆的效率相当。所有BALB/c淋巴结克隆均以剂量依赖方式对铜绿假单胞菌抗原产生增殖反应,且该反应受MHCⅡ类分子限制。相当一部分B6 T细胞克隆在无特异性抗原时也发生强烈增殖。根据干扰素-γ(IFN-γ)/白细胞介素-4(IL-4)的产生情况,来自这两种品系的淋巴结克隆可分为Th1或Th0。在任一小鼠品系中,从肺组织中克隆的效率均显著低于从淋巴结中克隆的效率,但与B6肺相比,从BALB/c肺中克隆的效率更高。对来自BALB/c的4个肺T细胞克隆和来自B6小鼠的2个肺T细胞克隆进行扩增以作进一步分析,结果观察到细胞因子产生存在品系间差异。两个B6肺T细胞克隆均类似Th1,产生IFN-γ但不产生IL-4和IL-10,而4个BALB/c肺T细胞克隆类似Th2,产生IL-4和IL-10但不产生IFN-γ。这些观察结果表明,肺中CD4+ Th反应的差异可能导致近交系小鼠品系对支气管肺部铜绿假单胞菌感染的抵抗力水平存在差异。