Appendix L. 
361 
and immunosuppression is required to prevent rejection. An 
important exception to this is observed in pregnant women who 
tolerate their unborn fetus despite the fact that it expresses a full set 
of non-matemal HLA antigens inherited from the father. The 
mechanisms by which embryonic tissue demonstrates immune 
privilege during prenatal development have not yet been fully 
elucidated, however it is evident that interactions between fetus and 
mother differ substantially from the events triggered by a classical 
allograft. Consequently, much work is being dedicated to the 
emerging field of matemo-fetal immunobiology in order to enable the 
development of innovative strategies to induce tolerance and prevent 
allogeneic graft rejection. 
When maternal T cells encounter the fetus they demonstrate 
adaptive tolerance. In part this may be due to the absence of 
expression of MHC class II antigens and low levels of expression of 
MHC class I antigens on fetal cells. However, this can only partly 
explain the state of prolonged maternal tolerance since induction of 
HLA class I and II molecules inevitably occurs as the fetus matures 
and differentiates, yet rejection still does not occur. Consequently, 
non-fetal aspects of the placental barrier must be of critical 
importance in maintaining prolonged tolerance to the fetus. An 
important mechanism may relate to upregulation of the human non- 
classical HLA class Ib antigen, designated HLA-G, by the 
syncytiotrophoblast. HLA-G molecules bind to inhibitory receptors 
on natural killer cells and subsequently protect against maternal 
rejection responses. The placenta produces high levels of the anti- 
inflammatory cytokine interleukin 10 which stimulates HLA-G 
synthesis while concomitantly downregulating MHC class I antigen 
production, thus contributing to the tolerance-inducing local 
environment. The trophoblast also produces high levels of the 
enzyme indoleamine 2,3-dioxygenase, which catabolizes tryptophan, 
an essential amino acid necessary for rapid T cell proliferation. 
Annexin II, found in isolated placental membranes in vitro is present 
in placental serum, exerts immunosuppressive properties, and 
additionally contributes to fetal allograft survival. Together, these 
features indicate that materno-fetal tolerance results from a 
combination of transiently reduced antigenicity of the fetus in 
combination with a complex tolerance-inducing milieu at the 
placental barrier. 
Immunogenic Characteristics Of Embryonic And Adult Stem Cells 
Murine and human embryonic stem (ES) cells do not express HLA 
class I and II antigens, and demonstrate reduced surface expression 
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