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

• Published in: Cellular immunology Vol. 154; no. 1; pp. 143 - 152
• Main Authors: Clark, David A., Chaouat, Gerard, Mogil, Rona, Wegmann, Thomas G.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.03.1994
• Subjects: Abortion, Spontaneous - immunology; Animals; Antibodies - pharmacology; CD8 Antigens; Cytotoxicity, Immunologic; Female; Fetal Resorption - immunology; Fetal Resorption - prevention & control; G(M1) Ganglioside - antagonists & inhibitors; G(M1) Ganglioside - immunology; Granulocyte-Macrophage Colony-Stimulating Factor - antagonists & inhibitors; Granulocyte-Macrophage Colony-Stimulating Factor - immunology; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Immune Tolerance; Killer Cells, Natural - immunology; Male; Mice; Mice, Inbred CBA; Mice, Inbred DBA; Pregnancy; T-Lymphocyte Subsets - immunology; Trophoblasts - immunology
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1006/cimm.1994.1064

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.