Kanzawa T, Sawada M, Kato K, Yamamoto K, Mori H, Tanaka R
Department of Neurosurgery, Niigata Brain Research Institute, Niigata University, Niigata, Japan.
J Neurosci Res. 2000 Nov 1;62(3):383-8. doi: 10.1002/1097-4547(20001101)62:3<383::AID-JNR8>3.0.CO;2-6.
We established granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent murine microglial clones and investigated the immune properties of four individual clones. All four clones expressed MHC class I and CD54 (ICAM-1) at similar levels. The 5-2, Ra2, and 6-3 clones expressed CD80 (B7-1), CD86 (B7-2), and MHC class II at low, medium, and high levels, respectively. Only the 6-3 clone expressed CD40. Generally, the levels of co-stimulation and CD 40 signals had a profound effect on the response to antigens. The 5-2, Ra2, and 6-3 clones, however, stimulated allogenic T-cell proliferation to the same extent or less compared to spleen cells. Although the 6-1 clone expressed co-stimulatory and MHC molecules at levels similar to Ra2, it suppressed allogenic T-cell proliferation, unlike Ra2. Thus, allo-antigen presentation by microglial clones was not correlated with the expression of CD40 and co-stimulatory molecules. When microglial clones were fixed with paraformaldehyde, they enhanced IL-2-dependent T-cell proliferation according to the level of their expression of co-stimulatory molecules. Furthermore, conditioned medium from the 6-1 clone inhibited the T-cell response to allo-antigen. This indicates that some factor(s) derived from a microglial subtype may play an important role in the regulation of T-cell proliferation in addition to the molecules involved in antigen presentation. Moreover, these results also suggest that there may be specialized subtypes of microglia that regulate the immune response in the CNS.
我们建立了粒细胞-巨噬细胞集落刺激因子（GM-CSF）依赖的小鼠小胶质细胞克隆，并研究了四个单独克隆的免疫特性。所有四个克隆均以相似水平表达MHC I类分子和CD54（细胞间黏附分子-1，ICAM-1）。5-2、Ra2和6-3克隆分别以低、中、高水平表达CD80（B7-1）、CD86（B7-2）和MHC II类分子。只有6-3克隆表达CD40。一般来说，共刺激水平和CD40信号对对抗原的反应有深远影响。然而，与脾细胞相比，5-2、Ra2和6-3克隆刺激同种异体T细胞增殖的程度相同或更低。尽管6-1克隆表达共刺激分子和MHC分子的水平与Ra2相似，但与Ra2不同，它抑制同种异体T细胞增殖。因此，小胶质细胞克隆的同种异体抗原呈递与CD40和共刺激分子的表达无关。当小胶质细胞克隆用多聚甲醛固定后，它们根据共刺激分子的表达水平增强了依赖白细胞介素-2的T细胞增殖。此外，6-1克隆的条件培养基抑制了T细胞对同种异体抗原的反应。这表明除了参与抗原呈递的分子外，源自小胶质细胞亚型的某些因子可能在T细胞增殖的调节中起重要作用。此外，这些结果还表明可能存在专门调节中枢神经系统免疫反应的小胶质细胞亚型。
