Grupo de Inmunología Celular e Inmunogenética, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia, Carrera 53 #61-30, Medellín, Colombia.
Tuberculosis (Edinb). 2012 Mar;92(2):148-59. doi: 10.1016/j.tube.2011.12.005. Epub 2012 Jan 5.
Mycobacterium tuberculosis DosR regulon-encoded proteins elicit strong immune T-cell responses in individuals with latent tuberculosis (LTBI). Also, resuscitation (Rpf) proteins can induce such responses. However, variations in the immunogenicity of the DosR and Rpf proteins have been observed in European and African populations, and no data are published from other geographic areas. In Colombian LTBI and patients with recently diagnosed PTB, we therefore studied the immune response to DosR, Rpf, stress, and nominal antigens from Mtb, in 7-day stimulated cultures. Three DosR (Rv1737c, Rv2029c, Rv2628c) and 2 Rpf (Rv0867 and Rv2389c) antigens were recognized most prominently on the basis of the net IFNγ production (DosR) or the percentage of responding individuals (Rpf). Results show that the selected DosR antigens induced a higher proportion of CD4-T cells producing IFNγ from LTBI, compared to pulmonary TB patients (PTB), while there were no differences in the proportion of CD8-T cells. An increased frequency of CD4, but not CD8 T-cells with a CD45RO(+)CD27(+) phenotype was observed in LTBI in response to Rv2029c, Rv0867c, and Rv2389c, compared to PTB. The levels of cytokines and chemokines in the supernatants of stimulated cells, showed that the DosR and Rpf antigens induced higher levels of IFNγ in cultures from LTBI compared to PTB, although the induced pattern of cytokines and chemokines was also antigen dependent. In summary, our results are consistent with the significant immunogenicity of Mtb DosR and Rpf antigens in LTBI individuals, and confirm and extend previously reported data from other TB affected human populations.
结核分枝杆菌 DosR 调控基因编码蛋白在潜伏性结核（LTBI）个体中引发强烈的免疫 T 细胞反应。此外，复苏（Rpf）蛋白也可以诱导这种反应。然而，在欧洲和非洲人群中观察到 DosR 和 Rpf 蛋白的免疫原性存在差异，并且没有来自其他地理区域的发表数据。因此，在哥伦比亚的 LTBI 和新近诊断为 PTB 的患者中，我们研究了在 7 天刺激培养物中，对 DosR、Rpf、应激和 Mtb 的名义抗原的免疫反应。根据净 IFNγ产生（DosR）或应答个体的百分比（Rpf），最突出地识别了 3 个 DosR（Rv1737c、Rv2029c、Rv2628c）和 2 个 Rpf（Rv0867 和 Rv2389c）抗原。结果表明，与肺结核患者（PTB）相比，所选 DosR 抗原从 LTBI 中诱导了更高比例的产生 IFNγ的 CD4-T 细胞，而 CD8-T 细胞的比例没有差异。与 PTB 相比，在 LTBI 中，对 Rv2029c、Rv0867c 和 Rv2389c 的反应中观察到 CD4，但没有 CD8 T 细胞的 CD45RO（+）CD27（+）表型的频率增加。与 PTB 相比，刺激细胞上清液中的细胞因子和趋化因子水平表明，DosR 和 Rpf 抗原在 LTBI 中的诱导水平高于 PTB，尽管诱导的细胞因子和趋化因子模式也依赖于抗原。总之，我们的结果与 Mtb DosR 和 Rpf 抗原在 LTBI 个体中的显著免疫原性一致，并证实和扩展了来自其他受结核病影响的人类群体的先前报道数据。
