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 mite 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-GMCSF 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. (C) 1994 Academic Press, Inc.