Khader Shabaana A, Partida-Sanchez Santiago, Bell Guy, Jelley-Gibbs Dawn M, Swain Susan, Pearl John E, Ghilardi Nico, Desauvage Frederic J, Lund Frances E, Cooper Andrea M
Trudeau Institute, Inc., Saranac Lake, NY 12983, USA.
J Exp Med. 2006 Jul 10;203(7):1805-15. doi: 10.1084/jem.20052545. Epub 2006 Jul 3.
Migration of dendritic cells (DCs) to the draining lymph node (DLN) is required for the activation of naive T cells. We show here that migration of DCs from the lung to the DLN after Mycobacterium tuberculosis (Mtb) exposure is defective in mice lacking interleukin (IL)-12p40. This defect compromises the ability of IL-12p40-deficient DCs to activate naive T cells in vivo; however, DCs that express IL-12p40 alone can activate naive T cells. Treatment of IL-12p40-deficient DCs with IL-12p40 homodimer (IL-12(p40)(2)) restores Mtb-induced DC migration and the ability of IL-12p40-deficient DCs to activate naive T cells. These data define a novel and fundamental role for IL-12p40 in the pathogen-induced activation of pulmonary DCs.
树突状细胞(DCs)迁移至引流淋巴结(DLN)是激活初始T细胞所必需的。我们在此表明,在缺乏白细胞介素(IL)-12p40的小鼠中,结核分枝杆菌(Mtb)感染后DCs从肺迁移至DLN存在缺陷。这种缺陷损害了IL-12p40缺陷型DCs在体内激活初始T细胞的能力;然而,仅表达IL-12p40的DCs能够激活初始T细胞。用IL-12p40同型二聚体(IL-12(p40)(2))处理IL-12p40缺陷型DCs可恢复Mtb诱导的DC迁移以及IL-12p40缺陷型DCs激活初始T细胞的能力。这些数据确定了IL-12p40在病原体诱导的肺DCs激活中的一种新的基本作用。