Prevention of spontaneous abortion in DBA/2-mated CBA/J mice by GM-CSF involves CD8+ T cell-dependent suppression of natural effector cell cytotoxicity against trophoblast target cells.
Spontaneous resorption (abortion) that occurs at a high rate in DBA/2-mated CBA/J female mice is dependent upon asialoGM1+ natural effector-type cells, can be ameliorated by alloimmunization or administration of GM-CSF, and is augmented by in vivo injection of anti-CD8 antibody. The abortion rate was similarly augmented by administration of monoclonal anti-GM-CSF neutralizing antibody, but the GM-CSF physiologically active in preventing abortion during normal pregnancy did not appear to be derived from maternal CB8+ T cells putatively responding to antigens on the fetoplacental unit. Rather, depletion of CD8+ cells in vivo prevented GM-CSF from reducing the rate of resorptions. GM-CSF administration rapidly downregulates natural effector cells able to kill a trophoblast target cell line in vitro, and anti-CD8+ antibody boosts total splenic cytotoxic cell activity. Further, anti-CD8 completely abrogated the ability of GM-CSF to suppress anti-trophoblast killer cell activity. These cells are known to be asialoGM1+ and injection of anti-asialoGM1 reduced the abortion rate appropriately in mice that had received anti-CD8. These data suggest that GM-CSF acts indirectly to prevent abortion in DBA/2-mated CBA/J mice through a mechanism that requires CD8+ maternal T cells, and systemic regulation of the level of anti-trophoblast killer cell activity may determine the success or failure of pregnancy in this system.
Clark
D A
DA
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Chaouat
G
G
Mogil
R
R
Wegmann
T G
TG
D000022:Abortion, Spontaneous / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016827:CD8 Antigens; D003602:Cytotoxicity, Immunologic; D005260:Female; D005327:Fetal Resorption / Q000276:immunology / Q000517:prevention & control; D005677:G(M1) Ganglioside / Q000037:antagonists & inhibitors / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D011247:Pregnancy; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014327:Trophoblasts / Q000276:immunology
D000906:Antibodies; D016827:CD8 Antigens; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D016178:Granulocyte-Macrophage Colony-Stimulating Factor