Recombinant human macrophage-colony stimulating factor suppresses the mouse mixed lymphocyte reaction.
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.
Sakurai
T
T
Biochemical Research Laboratory, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan.
Yamada
M
M
Simamura
S
S
Motoyoshi
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002455:Cell Division; D002460:Cell Line; D002474:Cell-Free System / Q000502:physiology; D002478:Cells, Cultured; D002850:Chromatography, Gel; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000737:chemistry / Q000166:cytology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D011994:Recombinant Proteins; D016753:Interleukin-10; D019323:omega-N-Methylarginine; D016173:Macrophage Colony-Stimulating Factor; D007213:Indomethacin