Procoagulants in fetus rejection: the role of the OX-2 (CD200) tolerance signal.
The spontaneous loss of normal karyotype embryos may be initiated or prevented by the maternal immune system. In mice, loss between the time of implantation (day 4.5) and formation of a vascularized placenta (day 9.5) when the embryo is too large to survive by diffusion alone, is analogous to occult pregnancy failure in humans. They are called occult because usually the woman does not know she is pregnant. From studies in mice, these early losses have a different mechanism than abortion of a vascularized placenta (analogous to clinically evident human spontaneous miscarriage). The latter depend on the activation of the novel prothrombinase fgl2 on the fetal trophoblast and in maternal decidua by the T helper-1 (Th1) type cytokines TNF- alpha+gamma -interferon that arise from NK cells and NK gammadelta T cells; conversion of prothrombin to thrombin which in turn generates IL8 that activates polymorphonuclear leukocytes leads to embryonic death. These inflammatory processes are counteracted by Th2/3-type cytokines that arise in part from V gamma 1 delta 6 T cells reacting to, as yet, unidentified trophoblast antigens in the presence of the 'tolerance signaling molecule' OX-2. By contrast, peri-implantation losses (between implantation and formation of a vascularized placenta, analogous to occult losses in humans) appear to be dependent upon perforin(+)cells, complement activation, and products of alphabeta T and NK alphabeta T cells, but not on TNF- alpha or procoagulant activation. Similarities and differences between findings in the mouse and human, and the potential evolutionary significance of mechanisms affecting reproductive success are reviewed.
Clark
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Departments of Medicine, Molecular Medicine & Pathology, Obstetrics & Gynecology, Mucosal Immunology Group, Immunology and Inflammation Program, McMaster University, Rm. 3V39, 1200 Main Street West, Hamilton, Ontario, L8N 3Z5, Canada. clarkd@mcmaster.ca
Yu
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Levy
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Gorczynski
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D000022:Abortion, Spontaneous / Q000276:immunology; D000818:Animals; D005075:Biological Evolution; D010064:Embryo Implantation / Q000276:immunology; D005260:Female; D005340:Fibrinogen / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D051379:Mice; D011247:Pregnancy; D013925:Thromboplastin / Q000276:immunology*; D014327:Trophoblasts / Q000276:immunology
C095202:FGL2 protein, human; C490637:Fgl2 protein, mouse; D005340:Fibrinogen; D013925:Thromboplastin