Giuliani A, Porcelli S A, Tentori L, Graziani G, Testorelli C, Prete S P, Bussini S, Cappelletti D, Brenner M B, Bonmassar E, Aquino A
Department of Neurosciences, University of Rome Tor Vergata, Italy.
Life Sci. 1998;63(12):985-94. doi: 10.1016/s0024-3205(98)00360-9.
Non-classical antigen-presentation by CD1 molecules expressed on cytokine-activated monocytes (CAM), and cell-mediated responses supported by double-negative (DN) and by CD8+ responder alphabeta T cells, are involved in host resistance against mycobacterial infections. The CD1b protein is responsible for presentation of non-peptide, lipid antigens to T cells. In this context, a pivotal role is played by induction of CD1b protein on the membrane of human monocytes activated by GM-CSF alone, and more efficiently by GM-CSF combined with IL-4. Rifampin (RFP), a drug which is extensively utilized for chemoprophylaxis or treatment of Mycobacterium tuberculosis, is known to reduce a number of B, or T cell-dependent responses. Therefore we undertook immunopharmacological studies on RFP, to determine the effects of this agent on human macrophage function, relative to antigen presentation by CD1b molecules and on DN T cell cytolytic function. The results showed that: (a) graded concentration of RFP (2 or 10 microg/ml) induced a significant increase of CD1b expression, in CAM as evaluated by FACS analysis; (b) RFP increased significantly the specific mAb binding to CD1b on CAM surface; (c) treatment of effector cells with RFP did not reduce DN T cell-mediated cytolysis against lymphoblastoid cells transfected with CD1b cDNA (C1R.b6 cells), pulsed with M. tuberculosis. These results suggest that RFP could be of potential value in improving mycobacterial antigen presentation without impairing responder T cell function.
细胞因子激活的单核细胞（CAM）上表达的CD1分子介导的非经典抗原呈递，以及由双阴性（DN）和CD8 +反应性αβ T细胞支持的细胞介导反应，参与宿主对分枝杆菌感染的抵抗力。CD1b蛋白负责将非肽脂质抗原呈递给T细胞。在这种情况下，单独由GM-CSF激活的人单核细胞膜上CD1b蛋白的诱导起着关键作用，而GM-CSF与IL-4联合使用时诱导作用更有效。利福平（RFP）是一种广泛用于预防或治疗结核分枝杆菌的药物，已知它会减少许多B细胞或T细胞依赖性反应。因此，我们对RFP进行了免疫药理学研究，以确定该药物对人巨噬细胞功能的影响，相对于CD1b分子的抗原呈递以及对DN T细胞溶细胞功能的影响。结果表明：（a）通过FACS分析评估，分级浓度的RFP（2或10μg/ml）诱导CAM中CD1b表达显著增加；（b）RFP显著增加了与CAM表面CD1b特异性结合的单克隆抗体；（c）用RFP处理效应细胞不会降低DN T细胞对用CD1b cDNA转染的淋巴母细胞（C1R.b6细胞）的溶细胞作用，这些细胞用结核分枝杆菌脉冲处理。这些结果表明，RFP在改善分枝杆菌抗原呈递而不损害反应性T细胞功能方面可能具有潜在价值。
