Presentation of exogenous antigens by macrophages: analysis of major histocompatibility complex class I and II presentation and regulation by cytokines.
Presentation of exogenous antigens by macrophages: analysis of major histocompatibility complex class I and II presentation and regulation by cytokines.
复制标题
巨噬细胞呈递外源抗原：分析主要组织相容性复合物 I 类和 II 类呈递以及细胞因子的调节。
DOI：
10.1002/eji.1830241024
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发表时间：
1994
影响因子：
5.4
通讯作者：
Rock,KL
中科院分区：
文献类型：
--
作者：
Kovacsovics-Bankowski,M;Rock,KL
淋巴器官中存在一种抗原提呈细胞（antigen presenting cell，APC），能将外源性抗原（antigen，Ag）与主要组织相容性复合体（major histocompatibility complex，MHC）Ⅰ类分子一起提呈。本研究开始分离这些APC的克隆，以明确地建立它们的表型并进一步研究它们的特性。小鼠骨髓巨噬细胞（BM MΦ）通过过表达mycandrafoncogenes而永生化。产生了五种BM MΦ细胞系，它们是吞噬细胞并且在它们的表面MΦ分化Ag处表达。所有五个细胞系的处理和提出外源性卵清蛋白（OVA）与MHC I类分子。它们都比可溶性Ag更有效地将OVA连接至吞噬底物102-104倍。两个MΦ细胞系的克隆分离株具有与未克隆细胞系相同的表型和功能特性。这些结果明确地证实了MΦ是具有呈递外源性Ag和MHC I类分子的能力的APC。干扰素（IFN）-γ白细胞介素-4、粒细胞-巨噬细胞集落刺激因子和脂多糖单独或联合诱导很少或没有增加，在某些情况下减少了外源性OVA与MHC I类的呈递。相反，所有MΦ激活因子均增加MHC I类分子的表达。此外，IFN-γ增加了胞质OVA的呈递，证明了胞质Ag与外源性Ag与MHC I类抗原之间的呈递差异。最后，一些细胞系组成型加工并呈现具有MHC II类的外源性OVA，而其他细胞系仅在用IFN-γ刺激后呈现。这些结果表明，参与外源性Ag与MHC I类和II类的呈递的途径是独立调节的，并且克隆细胞能够通过两种途径呈递外源性Ag。
There is an antigen presenting cell (APC) in the lymphoid organs capable of presenting exogenous antigen (Ag) with major histocompatibility complex (MHC) class I molecules. This study was initiated to isolate clones of these APC to definitively establish their phenotype and to further study their properties. Murine bone marrow macrophages (BM MΦ) were immortalized by overexpressingmycandrafoncogenes. Five BM MΦ cell lines were generated that are phagocytic and expressed at their surface MΦ differentiation Ag. All five cell lines processed and presented exogenous ovalbumin (OVA) with MHC class I molecules. They all presented OVA‐linked to a phagocytic substrate 102–104‐fold more efficiently than soluble Ag. Clonal isolates of two of the MΦ cell lines had an identical phenotype and functional properties as the uncloned lines. These results definitively establish that MΦ are APC with the capacity of presenting exogenous Ag with MHC class I molecules. Interferon (IFN)‐γ interleukin‐4, granulocyte‐macrophage colony stimulating factor and lipopolysaccharide either alone or in combination induced little or no augmentation and in some cases decreased presentation of exogenous OVA with MHC class I. In contrast, all of MΦ activating factors increased MHC class I expression. Moreover, IFN‐γ increased the presentation of cytosolic OVA, demonstrating differences between the presentation of cytosolic Ag versus exogenous Ag with MHC class I. Finally, some lines constitutively processed and presented exogenous OVA with MHC class II while others only presented after stimulation with IFN‐γ. These results demonstrate that the pathways involved in the presentation of exogenous Ag with MHC class I and class II are independently regulated and that a cloned cell is capable of presenting exogenous Ag through both pathways.