Flórido Manuela, Borges Margarida, Yagita Hideo, Appelberg Rui
Laboratory of Microbiology and Immunology of Infection, Institute for Molecular and Cell Biology, Portugal.
J Leukoc Biol. 2004 Nov;76(5):1039-46. doi: 10.1189/jlb.1103572. Epub 2004 Aug 17.
A panel of monoclonal antibodies specific for CD27 ligand (CD70), CD30 ligand (CD153), CD134 ligand (OX40L), and CD137 ligand (4-1BBL) were screened in vivo for their ability to affect the control of Mycobacterium avium infection in C57Bl/6 mice. Only the blocking of CD153 led to increased mycobacterial burdens. We then used CD30-deficient mice and found an increase in the proliferation of two strains of M. avium in these mice as compared with control animals. The increased mycobacterial growth was associated with decreased T cell expansion and reduced interferon-gamma (IFN-gamma) responses as a result of reduced polarization of the antigen-specific, IFN-gamma-producing T cells. At late times but not early in infection, the lymphoid cuff surrounding granulomas was depleted in the CD30-deficient animals. This report expands our knowledge about tumor necrosis factor superfamily members involved in the immune responses to mycobacterial infection by identifying CD30-CD153 interactions as required for optimal immune control of M. avium infection.
对一组针对CD27配体（CD70）、CD30配体（CD153）、CD134配体（OX40L）和CD137配体（4-1BBL）的单克隆抗体进行了体内筛选，以研究它们影响C57Bl/6小鼠体内鸟分枝杆菌感染控制的能力。只有阻断CD153会导致分枝杆菌负荷增加。然后我们使用了CD30缺陷小鼠，发现与对照动物相比，这两种鸟分枝杆菌菌株在这些小鼠中的增殖增加。分枝杆菌生长增加与T细胞扩增减少以及干扰素-γ（IFN-γ）反应降低有关，这是由于抗原特异性、产生IFN-γ的T细胞极化减少所致。在感染后期而非早期，CD30缺陷动物中肉芽肿周围的淋巴袖套减少。本报告通过确定CD30-CD153相互作用是鸟分枝杆菌感染最佳免疫控制所必需的，扩展了我们对参与分枝杆菌感染免疫反应的肿瘤坏死因子超家族成员的认识。
