Huygen K, Abramowicz D, Vandenbussche P, Jacobs F, De Bruyn J, Kentos A, Drowart A, Van Vooren J P, Goldman M
Instituut Pasteur van Brabant, Brussels, Belgium.
Infect Immun. 1992 Jul;60(7):2880-6. doi: 10.1128/iai.60.7.2880-2886.1992.
Three susceptible mouse strains, i.e., BALB/c (H-2d), C57BL/6 (H-2b), and major histocompatibility complex-congenic BALB.B10 (H-2b), were infected intravenously with 4 x 10(6) CFU of live Mycobacterium bovis BCG and analyzed 4 weeks later for in vitro spleen cell cytokine secretion in response to purified protein derivative (PPD), BCG culture filtrate (CF), BCG cellular extract, total BCG, the purified extracellular 30-32-kDa antigen (the fibronectin-binding antigen 85), or the intracellular 65-kDa heat shock protein. C57BL/6 and BALB.B10 mice produced 5- to 10-fold more gamma interferon and interleukin-2 (IL-2) when stimulated with CF, PPD, and antigen 85 than BALB/c mice did. When stimulated with BCG extract and whole BCG, gamma interferon and IL-2 levels were generally lower and comparable in the three strains. IL-4 was detected in spleen cell culture supernatants from infected BALB/c mice but not from C57BL/6 or BALB.B10 mice. IL-5 could not be detected. C57BL/6 and BALB.B10 spleen cells also produced more tumor necrosis factor alpha and IL-6 after stimulation with PPD and CF than BALB/c cells did. Finally, BCG vaccination generated efficient protective immunity in C57BL/6 and BALB.B10 mice but not in BALB/c mice. These data suggest that secreted mycobacterial CF antigens selectively induce a strong TH1 response in BCG-infected C57BL/6 and BALB.B10 mice, whereas in BALB/c mice this response is partly counterbalanced by TH2 cells.
三种易感小鼠品系，即BALB/c（H-2d）、C57BL/6（H-2b）和主要组织相容性复合体同基因的BALB.B10（H-2b），通过静脉注射4×10⁶CFU的活牛分枝杆菌卡介苗进行感染，并在4周后分析体外脾细胞对纯化蛋白衍生物（PPD）、卡介苗培养滤液（CF）、卡介苗细胞提取物、完整卡介苗、纯化的细胞外30 - 32 kDa抗原（纤连蛋白结合抗原85）或细胞内65 kDa热休克蛋白的细胞因子分泌情况。与BALB/c小鼠相比，C57BL/6和BALB.B10小鼠在用CF、PPD和抗原85刺激时产生的γ干扰素和白细胞介素-2（IL-2）多5至10倍。在用卡介苗提取物和完整卡介苗刺激时，γ干扰素和IL-2水平通常较低，且在这三种品系中相当。在感染的BALB/c小鼠的脾细胞培养上清液中检测到了IL-4，但在C57BL/6或BALB.B10小鼠中未检测到。未检测到IL-5。在用PPD和CF刺激后，C57BL/6和BALB.B10脾细胞产生的肿瘤坏死因子α和IL-6也比BALB/c细胞多。最后，卡介苗接种在C57BL/6和BALB.B10小鼠中产生了有效的保护性免疫，但在BALB/c小鼠中未产生。这些数据表明，分泌的分枝杆菌CF抗原在卡介苗感染的C57BL/6和BALB.B10小鼠中选择性地诱导强烈的TH1反应，而在BALB/c小鼠中，这种反应部分被TH2细胞抵消。
