Alloimmunization Against Well Defined Polymorphic Major Histocompatibility or Class I MHC Transfected L Cells Antigens Can Prevent Poly IC Induced Fetal Death in Mice

Abstract

These results indicate that defined MHC antigens can mediate fetal protection from induced fetal resorption, and suggest that one driving force in promoting MHC antigen polymorphism in mammals is their capacity to confer protection from NK mediated fetal demise.

Fetal-Specific CD8+ Cytotoxic T Cell Responses Develop during Normal Human Pregnancy and Exhibit Broad Functional Capacity

“…Alloreactive responses in this context are not necessarily detrimental, and uterine NK cells certainly have an important role in promoting uterine vascular remodeling. Indeed, allogeneic pregnancy has been suggested to offer a survival advantage compared with syngeneic pregnancy (53), and a relative lack of CD8 + T cell infiltration into decidua has been associated with pregnancy complications such as preeclampsia (54).…”

REVIEW ARTICLE: Tolerance to the Foetal Allograft?

“…19 Danger might explain why the CBA · DBA ⁄ 2 system is environmentally dependent, 20 although surprisingly, the LPS content of faeces does not correlate with abortion. 21 Danger, however, does not explain why CBA · DBA ⁄ 2 and DBA ⁄ 2 · CBA matings are seen differentially (gene imprinting experiments of A. Paldi) and why immunisation against paternal MHC antigens corrects 'danger', 22 even how immunisation permits pregnancy in case of donkey embryos implanted in mare (the donkey in horse pregnancy). 15 Finally, Matzinger did not envisage alloantigen-specific mechanisms regulating only the anti-foetal reactions.…”

REVIEW ARTICLE: Tolerance Mechanisms in Pregnancy: A Reappraisal of the Role of Class I Paternal MHC Antigens*

“…Poly I:C (and the more potent poly I:C12u) binds to tlr3 and triggers abortions (resorptions) in mouse strains such as C3H/HeJ, which lack tlr4 and which cannot be aborted by LPS 2–4 . In response to poly I:C12u, a variety of Th1 cytokines are overproduced, and NK‐lineage cells are activated.…”

“…In response to poly I:C12u, a variety of Th1 cytokines are overproduced, and NK‐lineage cells are activated. These cells adoptively transferred trigger abortion in untreated mice 2–4 Fig. 1a.…”

“…Any model of a successful (or unsuccessful) semi‐allogeneic pregnancy must take into consideration the role of paternal histocompatibility antigens. Non‐antigen‐specific tlr signals such as LPS or poly I:C can trigger a Th1 cytokine storm, activate NK‐lineage cells, activate the coagulation and complement system, and trigger pregnancy failure 2–7 . The presence of paternal alloantigens in the embryo can alter susceptibility to this process.…”