Mittrücker Hans-Willi, Steinhoff Ulrich, Köhler Anne, Krause Marion, Lazar Doris, Mex Peggy, Miekley Delia, Kaufmann Stefan H E
Department of Immunology, Max Planck Institute for Infection Biology, Caritéplatz 1, 10117 Berlin, Germany.
Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12434-9. doi: 10.1073/pnas.0703510104. Epub 2007 Jul 18.
Mycobacterium bovis bacille Calmette-Guérin (BCG) is the most widely used live bacterial vaccine. However, limited information is available correlating route and dose of vaccination and induction of specific T cell responses with protection against tuberculosis. We compared efficacy of oral and systemic vaccination and correlated vaccine-induced T cell responses with protection in experimental tuberculosis of mice. After oral and systemic vaccination, we observed profound differences in persistence and dissemination of BCG and frequencies and location of specific IFN-gamma-secreting CD4(+) and CD8(+) T cells. Yet, both vaccination routes caused comparable levels of protection against aerosol challenge with Mycobacterium tuberculosis. Protection correlated best with rapid accumulation of specific CD8(+) T cells in infected tissues of challenged mice. In contrast, specific IFN-gamma production by CD4(+) T cells reflected the load of M. tuberculosis rather than the strength of protection. Our data question the measurement of IFN-gamma secretion by CD4(+) T cells and emphasize the need for new biomarkers for evaluation of tuberculosis vaccine efficacies.
牛分枝杆菌卡介苗（BCG）是使用最广泛的活细菌疫苗。然而，关于疫苗接种途径和剂量以及特异性T细胞反应的诱导与结核病防护之间的关联，目前可获得的信息有限。我们比较了口服和全身接种疫苗的效果，并将疫苗诱导的T细胞反应与小鼠实验性结核病的防护相关联。口服和全身接种疫苗后，我们观察到卡介苗在持久性和传播以及特异性分泌干扰素-γ的CD4(+)和CD8(+) T细胞的频率和位置方面存在显著差异。然而，两种接种途径对结核分枝杆菌气溶胶攻击的防护水平相当。防护与受攻击小鼠感染组织中特异性CD8(+) T细胞的快速积累最相关。相比之下，CD4(+) T细胞产生的特异性干扰素-γ反映的是结核分枝杆菌的负荷而非防护强度。我们的数据对CD4(+) T细胞分泌干扰素-γ的测量提出了质疑，并强调需要新的生物标志物来评估结核病疫苗的效力。
