Sakurai T, Yamada M, Simamura S, Motoyoshi K
Biochemical Research Laboratory, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan.
Cell Immunol. 1996 Jul 10;171(1):87-94. doi: 10.1006/cimm.1996.0177.
We examined the effect of recombinant human macrophage-colony stimulating factor (rhM-CSF) on mouse macrophage accessory functions in vitro. The addition of rhM-CSF to an allogenic mixed lymphocyte culture (MLC) consisting of mouse spleen cells suppressed the proliferation of lymphocytes in a concentration-dependent manner. However, rhM-CSF did not suppress the mixed lymphocyte reaction (MLR) on the MLC that contained only purified T and dendritic cells. This suggested that the suppressive effect of rhM-CSF on the MLR occurs via spleen macrophages. Suppression of the MLR by rhM-CSF could not be neutralized by the addition of synthetic inhibitors of prostaglandin E2 (indomethacin) and nitric oxide (NG-mono-methyl-L-arginine). An antibody specific to mouse interleukin-10 (IL-10), which can neutralize the inhibitory effect of recombinant IL-10 in vitro, did not prevent rhM-CSF-induced suppression of the MLR. Even higher concentrations of IL-1 could not overcome the inhibitory effect of rhM-CSF. Moreover, culture supernatants of macrophages stimulated with rhM-CSF had a suppressive effect on the MLR. The concentrations of transforming growth factor beta (TGF-beta) and IL-10 in the suppressive culture supernatants were lower than those in the supernatants of nonstimulated macrophages. The supernatants suppressed the proliferation of the LBRM 33 TG6 mouse T cell line, but it did not affect the proliferation of other cell lines (L1210, L5178Y-R, and MC/9). These results suggest that rhM-CSF modulates a macrophage accessory function by stimulating macrophages to secrete a suppressive factor that causes suppression of the T cell response in vitro.
我们在体外研究了重组人巨噬细胞集落刺激因子（rhM-CSF）对小鼠巨噬细胞辅助功能的影响。向由小鼠脾细胞组成的同种异体混合淋巴细胞培养物（MLC）中添加rhM-CSF，以浓度依赖的方式抑制淋巴细胞的增殖。然而，rhM-CSF对仅含有纯化T细胞和树突状细胞的MLC中的混合淋巴细胞反应（MLR）没有抑制作用。这表明rhM-CSF对MLR的抑制作用是通过脾巨噬细胞发生的。rhM-CSF对MLR的抑制作用不能通过添加前列腺素E2（吲哚美辛）和一氧化氮（NG-单甲基-L-精氨酸）的合成抑制剂来中和。一种特异性针对小鼠白细胞介素10（IL-10）的抗体，其在体外可中和重组IL-10的抑制作用，但不能阻止rhM-CSF诱导的MLR抑制。即使更高浓度的IL-1也不能克服rhM-CSF的抑制作用。此外，用rhM-CSF刺激的巨噬细胞培养上清液对MLR有抑制作用。抑制性培养上清液中转化生长因子β（TGF-β）和IL-10的浓度低于未刺激巨噬细胞的上清液中的浓度。上清液抑制了LBRM 33 TG6小鼠T细胞系的增殖，但不影响其他细胞系（L1210、L5178Y-R和MC/9）的增殖。这些结果表明，rhM-CSF通过刺激巨噬细胞分泌一种抑制因子来调节巨噬细胞的辅助功能，该抑制因子在体外可导致T细胞反应的抑制。
