Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, Canada.
Immunol Cell Biol. 2010 Jan;88(1):3-12. doi: 10.1038/icb.2009.90. Epub 2009 Nov 24.
The initiation of T-cell immune responses requires professional antigen-presenting cells. Emerging data point towards an important role for macrophages (Mphi) in the priming of naïve T cells. In this study we analyzed the efficiency and the mechanisms by which Mphi derived from spleen (Sp-Mphi) or bone marrow (BM-Mphi) present Lymphocytic choriomeningitis virus (LCMV) antigens to epitope-specific T cells. We demonstrate that because of phagosomal maturation, Sp-Mphi downregulate their ability to cross-present cell-associated, but not soluble, antigens, as they are further differentiated in culture without altering their capacity to directly present virus antigens after infection. We propose that Sp-Mphi are extremely efficient at direct and cross-presentation. However, if these cells undergo further M-CSF-dependent maturation, they will adapt to be more scavenger and phagocytic and concurrently reduce their cross-presenting capacity. Accordingly, Sp-Mphi can have an important role in regulating T-cell responses through cross-presentation depending on their differentiation state.
T 细胞免疫应答的启动需要专业的抗原呈递细胞。新出现的数据表明，巨噬细胞（Mphi）在初始 T 细胞的启动中起着重要作用。在这项研究中，我们分析了源自脾脏（Sp-Mphi）或骨髓（BM-Mphi）的巨噬细胞向表位特异性 T 细胞呈递淋巴细胞性脉络丛脑膜炎病毒（LCMV）抗原的效率和机制。我们证明，由于吞噬体成熟，Sp-Mphi 下调了其呈递细胞相关但不呈递可溶性抗原的能力，因为它们在没有改变感染后直接呈递病毒抗原能力的情况下在培养中进一步分化。我们提出 Sp-Mphi 非常有效地进行直接和交叉呈递。然而，如果这些细胞经历进一步的 M-CSF 依赖性成熟，它们将适应成为更多的清道夫和吞噬细胞，同时降低其交叉呈递能力。因此，Sp-Mphi 可以通过交叉呈递根据其分化状态在调节 T 细胞应答方面发挥重要作用。
