Tolerance, suppression and the fetal allograft

Abstract

In solid organ transplantation the recipient immune system recognises foreign alloantigens expressed by the graft. This results in an immune attack of the transplanted organ leading to rejection, which can be prevented only by therapeutic immunosuppression. During pregnancy the fetus should also be rejected by the maternal immune system, since it expresses antigens derived from the father. Whilst the immune system retains the ability to respond to foreign antigen, tolerance mechanisms ensure that inappropriate responses against self-antigen are prevented. Maternal immune aggression directed against the fetus is partly inhibited by peripheral tolerance mechanisms that act locally to deplete cells capable of attacking the fetus. Other local mechanisms inhibit the pathways that cause tissue damage after immune activation. Recent studies in mice and humans indicate that the maternal immune system undergoes a more systemic change that promotes materno-fetal tolerance. Naturally occurring regulatory T cells, which are commonly associated with maintaining tolerance to self-antigens, can also suppress maternal allo-responses targeted against the fetus. We review the mechanisms that mediate materno-fetal tolerance, with particular emphasis on changes in regulatory T cell function during pregnancy and discuss their implications.

The role of the maternal immune system in the regulation of human birthweight

“…Adoptive transfer of CD8 þ T cells specific for H2-K b , to H2-K b -negative females carrying H2-K b -positive pups, did not result in pregnancy failure even though H2-K b is expressed on trophoblast [29,30]. However, expansion of Tregs is seen during both syngeneic and allogeneic pregnancies and depletion of Tregs during pregnancy results in fetal resorption only in allogeneic matings [31]. Tregs appear to play an important role in preventing rejection of allogeneic pregnancies but the exact mechanism is unclear.…”

Evidence for a Selective Migration of Fetus-Specific CD4+CD25bright Regulatory T Cells from the Peripheral Blood to the Decidua in Human Pregnancy

“…Fetal tissue can inhibit allogeneic immune responses by expressing IDO (that inhibits rapid proliferation of cells) (1,2), FAS ligand (that can cause apoptosis of activated cells that express FAS) (3), and complement inhibitory proteins to prevent complement activation (4). These mechanisms can inhibit immune responses at the fetal-maternal interface in an Ag-nonspecific manner (5).…”

Effects of Non-Inherited Parental Hla-Antigens Upon Immune Response in Progeny

“…Одним из таких возможных событий может быть совместимость супругов по HLA. Известно, что со вместимость супругов по HLA способствует подав лению репродуктивного иммунного ответа на гра нице между материнским микроокружением и клет ками плода [18,19,34]. Свободный переход совме стимых по HLA клеток матери и плода может спо собствовать либо толерантности, либо сенсибили зации по другим АГ (минорным MHC или эритро цитарным АГ).…”