Functional maturation of adult mouse resting microglia into an APC is promoted by granulocyte-macrophage colony-stimulating factor and interaction with Th1 cells
Functional maturation of adult mouse resting microglia into an APC is promoted by granulocyte-macrophage colony-stimulating factor and interaction with Th1 cells
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DOI：
10.4049/jimmunol.164.4.1705
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发表时间：
2000-02-15
影响因子：
4.4
通讯作者：
Adorini, L
中科院分区：
文献类型：
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作者：
Aloisi, F;De Simone, R;Adorini, L
诱导静息小胶质细胞成熟为有能力的APC的早期事件的精确知识可能有助于理解这种细胞类型在CNS免疫病理学发展中的参与，为了阐明来自预活化T细胞的信号是否足以诱导静息小胶质细胞中的APC特征，将来自成年BALB/c小鼠CNS的小胶质细胞与来自DO11.10 TCR转基因小鼠的Th 1和Th 2细胞系共培养，以检测APC相关分子和Ag呈递能力的调节。在Ag特异性与Th 1，但不是Th 2细胞的相互作用后，小胶质细胞强烈上调MHC II类，CD 40和CD 54分子的表面表达。小鼠小胶质细胞上CD 86的诱导不需要T细胞来源的信号。急性分离的成人小胶质细胞刺激Th 1细胞分泌IFN-γ，并在较小程度上，IL-2，但效率低下的刺激因子IL-4分泌的Th 2细胞。在体外暴露于IFN-γ的小胶质细胞表现出增强的MHC II类，CD 40和CD 54分子的表达，并能够重新刺激Th 2细胞。除IFN-γ外，GM-CSF增加了小胶质细胞活化Th 1细胞的能力，但不增加Th 2细胞的能力，而不上调MHC II类、CD 40或CD 54分子。这些结果表明，与Th 1细胞和/或Th 1分泌的可溶性因子的相互作用诱导成年小鼠小胶质细胞功能成熟为能够维持CD 4（+）T细胞活化的APC。此外，GM-CSF，T细胞以及反应性星形胶质细胞分泌的细胞因子，可以总理小胶质细胞的Th 1刺激能力，可能是通过提高他们的反应性Th 1衍生的信号。
A precise knowledge of the early events inducing maturation of resting microglia into a competent APC may help to understand the involvement of this cell type in the development of CNS immunopathology, To elucidate whether signals from preactivated T cells are sufficient to induce APC features in resting microglia, microglia from the adult BALB/c mouse CNS were cocultured with Th1 and Th2 lines from DO11.10 TCR transgenic mice to examine modulation of APC-related molecules and Ag-presenting capacity. Upon Ag-specific interaction with Th1, but not Th2, cells, microglia strongly up-regulated the surface expression of MHC class II, CD40, and CD54 molecules. Induction of CD86 on mouse microglia did not require T cell-derived signals. Acutely isolated adult microglia stimulated Th1 cells to secrete IFN-gamma and, to a lesser extent, IL-2, but were inefficient stimulators of IL-4 secretion by Th2 cells. Microglia exposed in vitro to IFN-gamma showed enhanced expression of MHC class II, CD40, and CD54 molecules and became able to restimulate Th2 cells. In addition to IFN-gamma, GM-CSF increased the ability of microglia to activate Th1, but not Th2, cells without up-regulating MHC class II, CD40, or CD54 molecules, These results suggest that interaction with Th1 cells and/or Th1-secreted soluble factors induces the functional maturation of adult mouse microglia into an APC able to sustain CD4(+) T cell activation. Moreover, GM-CSF, a cytokine secreted by T cells as well as reactive astrocytes, could prime microglia for Th1-stimulating capacity, possibly by enhancing their responsiveness to Th1-derived signals.